The administration of methotrexate in patients with Still's disease, "real-life" findings from AIDA Network Still Disease Registry.

OBJECTIVES: To describe clinical characteristics of patients with Still's disease treated with methotrexate (MTX) and to assess drug effectiveness evaluating change in disease activity, reduction of inflammatory markers, and glucocorticoid (GC)-sparing effect. METHODS: Patients with Still's disease treated with MTX were assessed among those included in AIDA Network Still Disease Registry. RESULTS: In this registry, 171 patients with Still's disease were treated with MTX (males 43.3%, age 37.1 ± 16.0 years). They were mainly characterised by joint features and fever without a prominent multiorgan involvement. MTX was administered with GCs in 68.4% of patients, with other conventional synthetic DMARDs in 6.4%, and with biologic DMARDs in 25.1%. A significant reduction of the modified systemic score was observed, and 38.6% patients were codified as being in clinical remission at the end of follow-up. The concomitant administration of a biologic DMARD resulted a predictor of the clinical remission. Furthermore, a reduction of inflammatory markers and ferritin levels was observed following the administration of MTX. Additionally, a marked reduction of the dosage of concomitant GCs was identified, while 36.7% discontinued such drugs. Male gender appeared as a predictor of GC discontinuation. MTX was discontinued in 12.3% of patients because of adverse effects, and in 12.3% for lack of efficacy. CONCLUSIONS: Clinical characteristics of patients with Still's disease treated with MTX were described, mainly joint features and fever without a prominent multiorgan involvement. The clinical usefulness of MTX was reported in reducing the disease activity, decreasing the inflammatory markers, and as GC-sparing agent.

Predictors of complete 24-month remission and flare in patients with polymyalgia rheumatica.

To date, few papers investigated the predictive factors of sustained 24-month remission and of flare in patients with polymyalgia rheumatica (PMR). We retrospectively evaluated clinical charts from PMR patients. Patients were evaluated at baseline, at 1 month, 3 months and subsequently at 6, 12 and 24 months. We analyzed the differences between patients who achieved remission within 6 months of diagnosis, those who achieved remission at 24 months, and patients who did not. Among 137 patients, 57 (41.6%) achieved remission at 6 months and complete remission at 24 months was achieved by 104 patients (75.9%). The erythrocyte sedimentation rate at baseline was higher in patients who did not achieve remission than in patients who achieved it (p = 0.012). Female patients were less likely to achieve complete remission (45/68, 66.2% vs. 59/69, 85.5%, p = 0.01) compared to males. Fifty-four patients (39.4%) experienced at least one flare. Patients who did not achieve sustained complete remission suffered a flare more often (22/39 vs. 32/98, p = 0.01) and earlier than patients who did (10.33 ± 7.89 months vs. 13.64 ± 6.97 months, p = 0.011). Multivariate analysis confirmed that female sex (RR = 3.2, 95% CI 1.3-7.9) and higher baseline prednisone dosage (RR = 1.1, 95% CI 1.007-1.109) were negative independent predictors of complete remission at 24 months. A significant percentage of patients with PMR requires prolonged steroid treatment and may experience flares at 24 months of follow-up. Female sex and higher baseline prednisone dosage are negative independent predictors of complete remission at 24 months.

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.

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.

Development and Implementation of the AIDA International Registry for Patients With Still's Disease.

Objective: Aim of this paper is to present the design, construction, and modalities of dissemination of the AutoInflammatory Disease Alliance (AIDA) International Registry for patients with systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD), which are the pediatric and adult forms of the same autoinflammatory disorder. Methods: This Registry is a clinical, physician-driven, population- and electronic-based instrument implemented for the retrospective and prospective collection of real-world data. The collection of data is based on the Research Electronic Data Capture (REDCap) tool and is intended to obtain evidence drawn from routine patients' management. The collection of standardized data is thought to bring knowledge about real-life clinical research and potentially communicate with other existing and future Registries dedicated to Still's disease. Moreover, it has been conceived to be flexible enough to easily change according to future scientific acquisitions. Results: Starting from June 30th to February 7th, 2022, 110 Centers from 23 Countries in 4 continents have been involved. Fifty-four of these have already obtained the approval from their local Ethics Committees. Currently, the platform counts 290 users (111 Principal Investigators, 175 Site Investigators, 2 Lead Investigators, and 2 data managers). The Registry collects baseline and follow-up data using 4449 fields organized into 14 instruments, including patient's demographics, history, clinical manifestations and symptoms, trigger/risk factors, therapies and healthcare access. Conclusions: This international Registry for patients with Still's disease will allow a robust clinical research through collection of standardized data, international consultation, dissemination of knowledge, and implementation of observational studies based on wide cohorts of patients followed-up for very long periods. Solid evidence drawn from "real-life" data represents the ultimate goal of this Registry, which has been implemented to significantly improve the overall management of patients with Still's disease. NCT05200715 available at https://clinicaltrials.gov/.

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.

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 association between body mass index and fibromyalgia severity: data from a cross-sectional survey of 2339 patients.

OBJECTIVE: Various studies have shown that overweight and obesity are central features of FM, but the real impact of a high BMI on clinical severity in patients with FM is still controversial. The aim of this study was to analyse the relationships between BMI categories and measures of symptom severity and functional impairment using data from a Web-based registry of patients with FM. METHODS: Adult patients with an ACR 2010/2011 diagnosis of FM underwent a complete physical examination and laboratory tests and were asked to complete a package of questionnaires covering their sociodemographic and treatment details, in addition to the following disease-specific questionnaires: the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromyalgia Assessment Status questionnaire (ModFAS) and the Polysymptomatic Distress Scale (PDS). RESULTS: A total of 2339 patients were recruited and divided into two weight categories, underweight/normal (U/N, n = 1127, 48.2%) and overweight/obese (O/O, n = 1212, 51.8%). The total and subscales of FIQR, ModFAS and PSD scores were significantly higher in the O/O patients, as were all the mean scores of the individual FIQR items (P < 0.001 for all). CONCLUSION: Our findings demonstrate that O/O patients with FM are significantly more impaired than U/N patients in all the symptomatological and functional domains as measured using the FIQR, ModFAS and PDS, thus suggesting that being O/O has an additional effect on symptoms and function.

Contribution of Janus-Kinase/Signal Transduction Activator of Transcription Pathway in the Pathogenesis of Vasculitis: A Possible Treatment Target in the Upcoming Future.

Janus-kinase (JAK) and signal transduction activator of transcription (STAT) signal transduction pathway is involved in a wide range of physiological and pathological processes, including in the pathogenesis of several autoimmune diseases. Data supporting the role of JAK/STAT in the development of vasculitis are limited and mostly focused on large vessel vasculitis and Behçet's disease. In this review, we provide a thorough picture of currently available evidence on the topic, gathered from in vitro experiments, animal models and human real-life data, analyzing the rationale for the use of JAK inhibitors for the management of vasculitis. Overall, despite a very strong biological and pathogenic basis, data are too few to recommend this therapeutic approach, beyond very severe and refractory forms of vasculitis. However, for the same reasons, a strong scientific effort in this direction is indeed worthwhile.

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.

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.

One year in review 2020: comorbidities, diagnosis and treatment of primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is a complex and heterogeneous disorder characterised by a wide spectrum of glandular and extra-glandular features. The discovery of novel biomarkers allowed to characterise the disease not only phenotypically on the basis of clinical presentation, but also on the basis of the endotype. Moreover, a better stratification of patients has important value in the evaluation of mechanisms underlying the risk of lymphoproliferative disorders in these patients. Finally, novel targeted therapies may open new possibilities for the application of personalised medicine in pSS.

High risk of early conversion to multiple sclerosis in clinically isolated syndromes with dissemination in space at baseline.

INTRODUCTION: Multiple sclerosis (MS) usually presents at onset with a clinically isolated syndrome (CIS). According to 2010 McDonald criteria, a diagnosis of MS can be made if CIS patients satisfy clinical/MRI criteria of both dissemination in time (DIT) and space (DIS). OBJECTIVE: The aim of this study was to analyze the follow-up data and possible prognostic factors of CIS patients satisfying DIS MRI criteria. PATIENTS AND METHODS: We performed a retrospective, multicenter study across 2 Italian centers. Clinical, MRI, and laboratory assessments were performed according to real-life clinical workup. RESULTS: Out of the 137 enrolled patients, during a median follow-up time of 3.1years, 116 (84.7%) converted to MS with the large majority (78.4%) of the converters developing MS within 1year. In multivariate analysis, baseline predictors of an earlier conversion were a cerebellar/brainstem CIS (HR 2.00, 95% CI: 1.3-3.0, p=0.001) and the presence of all the Barkhof-Tintore MRI criteria (HR 1.67, 95% CI: 1.1-2.6, p=0.028). CONCLUSIONS: Patients with CIS and DIS are at very high risk of an early conversion to MS. The onset with cerebellar/brainstem symptoms and the evidence of a higher MRI lesion load at baseline are the strongest independent predictors of an early conversion to MS.