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IntroductionBased on ACR/EULAR classification criteria, minor salivary glands biopsy (MSGB) is a useful diagnostic tool for the diagnosis of primary Sjögren’s syndrome (SS). The main objective of our study was to evaluate the diagnostic role of MSGB, as well as to highlight correlations between histological findings and autoimmune profiles.Material and methodsWe retrospectively evaluated histological and autoimmunity data from patients who underwent MSGB in our department in cases of suspected SS, from March 2011 to December 2018. Salivary gland samples were evaluated using Chisholm and Mason (CM) grading and the focus score (FS).ResultsA total of 1,264 patients (108 males, 1,156 females) were included. The median age was 55.22 ±13.51 years (range: 15–87). In univariate binary logistic regression, CM ≥ 3 and FS ≥ 1 were significantly predicted by antinuclear antibodies (ANA), anti-extractable nuclear antigens (ENA) and anti-Ro/SSA titer as well as anti-La/SSB, anti-Ro/SSA, rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) positivity. In multivariate analysis, CM ≥ 3 and MSGB positivity were significantly associated with ANA titer; FS ≥ 1 was not associated with laboratory findings. A positive biopsy was associated with laboratory findings, as ANA and ENA titers, anti-Ro/SSA, anti-La/SSB, RF and ACPA positivity may discriminate patients with SS-related histological findings.ConclusionsMinor salivary glands biopsy is a useful tool to diagnose SS in cases of highly suggestive clinical symptoms but in the absence of a specific autoimmunity.

Objectives No clear-cut guidelines exist for the use of imaging procedures for the diagnosis of idiopathic inflammatory myopathies (IIM). The aim of the present study was to assess the diagnostic accuracy of power Doppler ultrasonography (PDUS) score in IIM patients compared with a control group and its usefulness during follow-up. Methods All patients evaluated in the Vasculitis and Myositis Clinic, Rheumatology Unit, University of Siena were prospectively collected. All patients underwent US examination of both thighs in axial and longitudinal scans, which were also performed twice (T1) or three times (T2). Results Forty-five patients with IIM (median [interquartile range] age 55 [45–66] years; 35 female) were enrolled. Receiver operating characteristic curves distinguished patients and controls based on ∑power Doppler (PD), ∑oedema, ∑atrophy and CRP. The best cut-off value for ∑PD was 0.5, ∑oedema 1.5, ∑atrophy 0.5 and CRP 0.22 mg/dl. In a logistic regression analysis, the variables that most influenced diagnosis of IIM were ∑PD and ∑oedema (P = 0.017 and P = 0.013, respectively). ∑Oedema was lower at T1 (P = 0.0108) and T2 (P = 0.0012) than at T0. Likewise, ∑PD was lower at T1 (P = 0.0294) and T2 (P = 0.0420) than at T0. Physician global assessment was lower at T1 (P = 0.0349) and T2 (P = 0.0035) than at baseline. Conclusion Our findings show that PDUS is a reliable diagnostic tool in the differential diagnosis between inflammatory and non-inflammatory myopathies. Moreover, PDUS can be employed also during the follow-up of patients with IIM. A reduction in disease activity, measured by physician global assessment, led to a concomitant decrease in both oedema and PD, which was directly correlated with their rate of change. This underlines the close link between clinical assessment and PDUS findings, not only at diagnosis but also during monitoring.

OBJECTIVES To investigate peripheral enthesitis with power Doppler ultrasound (PDUS) in patients presenting low back pain (LBP) and metabolic syndrome (MetS) in comparison with patients with only LBP, to correlate US scores with clinical-anthropometric characteristics, and to define any relationship between enthesitis and concurrent diffuse idiopathic hyperostosis syndrome (DISH). METHODS Sixty outpatients with LBP and MetS, evaluated with multi-site entheseal PDUS, scoring inflammatory and structural damage changes, were retrospectively analyzed. A group of 60 subjects with LBP, without MetS and evaluated with the same protocol, was analyzed as the control group. RESULTS Patients showed overweight (BMI 29.8) and low-grade inflammatory state (C-reactive protein [CRP] 0.58mg/dL, erythrosedimentation rate [ESR] 20.2mm/h). Enthesitis was demonstrated in 52 (86%) patients (17.6% entheses), and in 8 controls (13.3%) (p

IntroductionOsteoporosis is the most represented metabolic bone disease and is characterized by the reduction of bone mineral density (BMD), exposing patients to high fracture risk and disability. Bisphosphonates (BPs) are the main compounds exploited in treatment of osteoporosis and significantly reduce fracture risk. Sarcopenia is the pathological reduction of muscle masses and strength, and many studies highlighted its co-existence in patients with impaired bone mass. Indeed, the pathological reduction of lean tissue has been linked to a higher risk of falls and, consequently, fractures and disability. Moreover, the pathological reduction of lean tissue seems to share many pathological mechanisms with impaired bone strength and structure; thus, in this context, we decided to conduct a retrospective case-control study aimed at evaluating the effects of BPs on lean mass and body composition.Material and methodsWe enrolled postmenopausal women from our metabolic bone diseases outpatient clinic who underwent at least two consecutive dual-energy X-ray absorptiometry (DXA) examinations concomitantly to the beginning of an antiresorptive agent. The body composition of patients and controls was compared by fat masses, lean masses and android-to-gynoid ratio (A/G ratio).ResultsA total of 64 female subjects were considered for the study: 41 starting a BP and 23 without treatment were used as control. The fat masses and lean masses appeared to be unaffected by BPs. Conversely, A/G ratio was lower in BPs group after 18 months of therapy compared to baseline (pConclusionsBisphosphonates treatment did not modify lean tissues, however a significant reduction of A/G ratio in BP group was documented. Thus the BPs seems to act on patients body composition and extra-skeletal tissues but larger prospective studies are needed to evaluate whether these modifications have clinical relevance.

Objectives: To evaluate the impact of obesity in patients with adult onset Still's disease (AOSD) and to assess their clinical characteristics and disease outcomes. Methods: The clinical features of AOSD patients with a body mass index (BMI) ≥ 30 were assessed among those included in the multicentre Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort. Results: Out of 139 AOSD patients, who had BMI registered in our database, 26 (18.7%) had a BMI ≥ 30. A lower rate of sore throat (P

Objective Several studies show that age at onset has an impact on the clinical-serological presentation, comorbidities and disease course of patients with systemic lupus erythematosus (SLE). We evaluated whether, in patients with recent onset SLE, the age at onset correlates with clinical-serological manifestations and with comorbidities. Methods We analysed 171 patients with a SLE diagnosis obtained within 12 months of diagnosis enrolled in the Early Lupus project. Based on the age of onset of the first disease symptom, they were stratified into 2 groups: early onset (18–45 years) and late onset (>45 years). The analysis was replicated by stratifying patients based on age at diagnosis (fulfillment of ACR classification criteria). Each comparison was made at baseline and at 36 months of follow-up. Results Baseline: patients with late onset displayed comorbidities (hypertension, dyslipidaemia and osteoporosis) more frequently than early onset group. 11.4% of late onset patients had a malignancy in medical history, not recorded in the early onset cohort. The two groups differed neither in organ involvement (domain BILAG) nor in disease activity (ECLAM). Patients with early onset showed a disease with signs of higher serologic activity (higher frequency of anti-dsDNA positivity and lower mean C3 and C4 levels) and had malar rash more frequently than the late onset group (36.2% vs. 18.2%, p=0.042). Similar results were obtained by stratifying patients by age of diagnosis (18-45 years and >45 years), except for the higher frequency of discoid rash in the group with age at diagnosis >45 years (18% vs. 6.6%, p=0.045). 36 months: the 2 groups of patients independently of the stratification applied did not differ in the accumulation of damage, but showed a different pattern of 8 organ involvement. Musculoskeletal involvement was more frequent both in the late onset group (18.6% vs. 7.3%, p=0.043) and in the group with age at diagnosis >45 years (20.4% vs. 5.9%, p=0.009) compared to their counterparts, while renal involvement was more frequent in the group with age at diagnosis 18–45 years (21.4% vs. 6.1%, p=0.03).A sub analysis at 36 months on patients without hypertension and osteoporosis at enrollment showed that patients with older age at onset had a higher frequency of these comorbidities, compared to their counterparts. Conclusion In our cohort, younger disease SLE onset seems to correlate with a more active immunological profile, while late onset with a higher incidence of comorbidities.

© 2022 Elsevier Inc.Background/objectives: Long-term efficacy and safety of tocilizumab (TCZ) in adult-onset Still's disease (AOSD) mostly derive from small case series. Herein we report a registry-based study investigating TCZ efficacy and safety in a cohort of patients with AOSD evaluated by clinical and serum inflammatory markers as well as drug retention rate analysis. Methods: This is an international multicentre study analyzing data from patients with AOSD regularly enrolled in the AIDA registry. TCZ efficacy was evaluated between baseline and last follow-up assessment in terms of changes in the Pouchot score and laboratory findings. Drug-retention rate was estimated by the Kaplan-Meier method, while Cox-regression analysis was employed to detect potential predictive factors of treatment withdrawal. Results: Data from 31 patients (15 men, 16 women) refractory to the conventional therapies and treated with TCZ were extracted from the AIDA registry. Mean ± SD time of treatment duration with TCZ was 24.32 ± 20.57 months. Median (IRQ) Pouchot score significantly decreased throughout the study period (p=0.001) with a significant difference between baseline [2.00 (4.00)] and 6 month-follow-up [0.00 (0.00)] (p=0.003) and between baseline and last follow-up assessment [0.00 (0.00)] (p=0.032), while no differences were observed between 6 month-evaluation and last follow-up assessment (p=0.823). Similarly, laboratory parameters significantly decreased from baseline to the last follow-up visit. With regard to drug survival, cumulative TCZ retention rate at 12-, 24-, and 36-month follow-up visit were 83.1%, 71.7% and 63.7%, respectively, without significant differences between biologic naïve patients and those previously treated with other biologics (p=0.329). Likewise, no significant differences were observed between chronic articular course of AOSD and other types of disease course (p=0.938) or between patients co-administered with conventional immunosuppressants and patients receiving TCZ as monotherapy (p=0.778). Cox-regression analysis identified no variable associated with a higher hazard of treatment withdrawal. Treatment was discontinued in 9 patients due to long-term remission (n=4), adverse events (n=2), loss of efficacy (n=1), non-medical reason (n=1) and unspecified cause (n=1). Mean glucocorticosteroids daily dose significantly decreased from baseline (18.36 ± 24.72 mg) to the last follow-up assessment (4.02 ± 4.99 mg, p=0.003). Conclusions: TCZ allows control of disease activity as well as normalization of serum inflammatory markers in both systemic and chronic articular form of AOSD. Additionally, TCZ displays an excellent drug retention rate while minimizing the risk of long-term exposure to corticosteroids.

Giant cell arteritis (GCA) is a large-vessel vasculitis, typically affecting the aorta and its branches. The involvement of vertebral and internal carotid arteries occurs in a limited number of cases, and stroke as a presenting symptom of GCA is extremely unusual: this subset of the disease has a poor prognosis and rarely responds to immunosuppression. We report the case of a 70-year-old woman, who presented to the Emergency Department for ische­mic stroke, which appeared to be the first and only symptom of GCA. The prompt administration of steroids and tocilizumab (TCZ) led to clinical and radiological resolution, with no residual disability at 6-month follow-up. Our case-based review, highlighting the rarity of a large vessel vasculitis presenting only with a cerebrovascular accident, provides new evidence for the efficacy of TCZ even in more unusual varieties of GCA: in these cases, TCZ should be immediately prescribed, in order to prevent mortality and severe long-term morbidity.

IntroductionBone loss is a common feature in several autoimmune and chronic inflammatory diseases, such as rheumatoid arthritis (RA). Indeed, the high levels of pro-inflammatory cytokines seem to enhance bone resorption and to diminish bone formation, thus producing an uncoupling between osteoclast and osteoblast function and favoring the onset of juxtarticular as well as systemic osteoporosis. Many papers underline the high prevalence of osteoporosis in RA, as well as the negative correlation between interleukin 6 (IL-6) serum levels and bone mineral density (BMD). The aim of this study was to assess the effectiveness of one-year treatment with tocilizumab (TCZ), the first approved IL-6 receptor inhibitor, in reducing bone loss in RA.Material and methodsWe enrolled 18 patients fulfilling 2010 ACR and EULAR criteria for RA from our arthritis outpatient clinic, assessing clinical and biochemical parameters during a 12-month period. The patients received TCZ 8 mg/kg i.v. every 4 weeks and underwent dual energy X-ray absorptiometry (DXA) for the measurement of bone mineral density (BMD) at baseline and at the end of study. Serum levels of C-reactive protein (CRP), erythrocytes sedimentation rate (ESR), IL-6, serum CrossLaps, osteoprotegerin (OPG), receptor activator of nuclear factor κβ ligand (RANK-L) and dickkopf-1 (DKK-1) were measured at baseline, at 6 months and 1 year.ResultsNo significant difference in IL-6, RANK-L, DKK-1, OPG and serum CrossLaps levels between baseline, 6 months and 1 year were found. A significant increase of lumbar spine BMD was evidenced after 1 year of TCZ treatment. No difference in total body and femoral neck BMD was documented the end of the study.ConclusionsThis study suggest the bone-sparing effect of TCZ in RA affected individuals.

IntroductionTo evaluate differences of injection related pain, and the accuracy of the techniques in two groups of overweight patients, performing the anterolateral approach for one group (G1) and the superolateral approach for the second group (G2).Material and methodsIn the study, 126 knee joints from 86 osteoarthritis (OA) patients were evaluated. Inclusion criteria were body mass index (BMI) ≥ 25, absence of effusion and coagulopathy. Pain evaluation during injection was evaluated with Visual Analogue Scale (VAS), while accuracy of the procedure was evaluated with ultrasound (US).ResultsThe patients’ mean age was 69.9 ±9.01, VAS for G1 group was 1.71 ±1.89, for G2 group was 1.74 ±1.31. Mean BMI was 29.69 ±2.86, for G1 group was 28.29 ±3.29, for G2 group was 30.32 ±2.41. No adverse events (AE) occurred in both studied groups. The accuracy rate of the procedure was 69.1% for G1 (38/55 knees), 95.7% for G2 (68/71 knees). No significant difference was found in VAS pain score between G1 and G2 group (p = 0.45). We found the significant correlation between BMI and VAS pain score in anterolateral accesses (G1) (r = 0.51; p < 0.005). No correlation was found between age and VAS pain score in anterolateral access (G1). For the superolateral access (G2), no correlation was found for age or BMI and VAS pain score.ConclusionsHyaluronic acid injection is safe therapeutic option for knee OA with no significant differences between anterolateral and superolateral approaches in terms of pain in overweight patients. However, higher BMI seems to be a predictor of pain in anterolateral access, and the superolateral approach should be preferred in this group of patients.

Purpose: The purpose of this study was to evaluate the prevalence and the underreporting rate of sacroiliitis (SI) in a large cohort of patients with biopsy-proved Crohn&rsquo, s disease (CD) who underwent magnetic resonance enterography (MRE) or computed tomography enterography (CTE). Materials and Methods: Patients with CD were recruited from eight Italian health centers in the period from January 2013 to December 2017. Disease activity was recorded according to the CD activity index (CDAI). The scans were read by two blinded readers who defined the presence of SI according to Assessment of SpondyloArthritis International Society (ASAS) classifications and European League Against Rheumatism (EULAR) recommendations. Moreover, SI was scored using a simplified Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system. Results: Interobserver agreement in diagnosing SI on imaging was good (K = 0.72&ndash, 0.83). SI was diagnosed in 129 (14.4%, 54 men, 75 women) out of 894 patients, however, sacroiliac joint (SIJ) abnormalities were not mentioned in the radiological reports of 112 patients (86%). Fifty (38.7%) out of 129 patients also underwent a subsequent SIJ evaluation through a dedicated MRI protocol to confirm SI. SI was found in a higher percentage of patients with &ldquo, active&rdquo, than &ldquo, inactive&rdquo, CD (18% vs. 4%). Conclusion: This study confirms the feasibility of CTE and MRE for the screening of SI in CD patients, however, it also underlines the remarkable problem concerning the underreporting of this entity in radiological practice.

Objectives The efficacy and safety of certolizumab pegol (CZP), an Fc-free, PEGylated anti-TNF, in axial spondyloarthritis (axSpA) has been established in clinical trial settings. We report CZP effectiveness and safety in European clinical practice in patients with axSpA, including radiographic (r-) and non-radiographic (nr-) axSpA. Methods CIMAX (NCT02354105), a European non-interventional multicentre prospective study, observed CZP treatment response and safety over 12 months in a real-world axSpA cohort. The primary outcome was change from baseline in BASDAI to week 52, with additional outcomes pertaining to effectiveness and safety. Patients who received ≥1 dose CZP were followed up for adverse events, and those with baseline and ≥1 post-baseline BASDAI assessment were included in effectiveness analyses. Results A total of 672 patients (r-axSpA: 469; nr-axSpA: 201; unconfirmed diagnosis: 2) from 101 sites received ≥1 dose of CZP, of whom 564 (r-axSpA: 384; nr-axSpA: 179; unconfirmed: 1) were included in the effectiveness analyses. The mean baseline BASDAI was 6.1 in the overall axSpA population and r-axSpA and nr-axSpA subpopulations. At week 52, the mean (s.d.) change in BASDAI was −2.9 (2.3; n = 439); for r-axSpA and nr-axSpA, it was −2.9 (2.2; n = 301) and −2.8 (2.4; n = 137), respectively (P Conclusion Improvements observed in signs and symptoms of axSpA following one year of CZP treatment in real-world clinical practice were similar to those from previous randomized clinical trials, with no new safety concerns.

Gitelman syndrome (GS) is an inherited salt-wasting tubulopathy characterized by hypocalciuria, hypokalemia, hypomagnesemia and metabolic alkalosis, due to inactivating mutations in the SLC12A3 gene. Symptoms may be systemic, neurological, cardiovascular, ophthalmological or musculoskeletal. We describe a 70 year-old patient affected by recurrent arthralgias, hypoesthesia and hyposthenia in all 4 limbs and severe hypokalemia, complicated by atrial flutter. Moreover, our patient reported eating large amounts of licorice, and was treated with medium-high dosages of furosemide, thus making diagnosis very challenging. Genetic analysis demonstrated a novel heterozygous mutation in the SLC12A3 gene; therefore, we diagnosed GS and started potassium and magnesium replacement. GS combined with chondrocalcinosis and neurological involvement is quite common, but this is the first case of an EMG-proven severe neuropathy associated with GS. Herein, we underline the close correlation between hypomagnesemia, chondrocalcinosis and neurological involvement. Moreover, we report a new heterozygous mutation in exon 23 (2738G>A), supporting evidence of a large genetic heterogeneity in this late-onset congenital tubulopathy.

Interstitial lung disease (ILD) has been described as a possible pulmonary involvement in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV), mainly granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Aim of this cross-sectional Italian national study was to describe demographic, clinical and serological profile of ILD related to MPA and GPA and investigate possible correlations between radiologic patterns of ILD and vasculitis features.We enrolled 95 consecutive patients with AAV-ILD, 56 affected by MPA (58.9%) and 39 by GPA (41.1%).NSIP was the most frequently detected ILD pattern, observed in c-ANCA patients in 60.9% of cases, followed by UIP pattern mainly observed in p-ANCA patients (47.7%, p=0.03). ILD represented the first clinical manifestation, preceding vasculitis diagnosis in 22.1% of cases and, globally, ILD was already detectable at AAV diagnosis in 66.3% of patients. The diagnosis of ILD preceded that of AAV in 85.7% of p-ANCA positive-patients, while only one patient with c-ANCA developed ILD before AAV (p= 0.039). Multivariate analysis confirmed the correlation of UIP pattern with p-ANCA-positivity and a diagnosis of ILD before AAV, also when adjusted for age and sex.Our study confirms that UIP is a frequent pattern of lung disease in AAVILD patients. Our results also suggest that ILD can represent an early complication of AAV but also occur in the course of the disease, suggesting the need of a careful evaluation by both pulmonologist and rheumatologist to achieve an early diagnosis. Further prospective studies are needed to define ILD prevalence and evolution in AAV patients.

Objective In this study, we aimed to describe the clinical characteristics, life-threatening complications occurrence, and mortality of adult-onset Still's disease (AOSD) patients with elderly onset. Methods A multicentre retrospective study of prospectively followed-up AOSD patients included in Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort was performed. Results Out of 221 assessed patients, 37 (16.7%) had an onset of the disease aged over 60 years. When compared with younger patients, these were characterised by a higher prevalence of pericarditis (p=0.008), comorbidities (p < 0.0001), and mortality (p=0.023). Age predicted the presence of serositis in both univariate (HR: 1.02, 95%CI: 1.01-1.03, p=0.007) and multivariate analyses (HR: 1.02, 95%CI: 1.01-1.04, p=0.007). Age was also a significant predictor of parenchymal lung disease in both univariate (HR: 1.03, 95%CI: 1.01-1.05, p=0.017) and multivariate analyses (HR: 1.03, 95%CI: 1.00-1.05, p=0.048). Furthermore, age resulted to be a negative predictor of polycyclic pattern only in univariate analysis (HR: 0.99, 95%CI: 0.97-1.00, p=0.048). Finally, age significantly predicted the mortality in both univariate (HR: 1.03, 95%CI: 1.00-1.06, p=0.034) and multivariate analyses (HR: 1.05, 95%CI: 1.01-1.08, p=0.012). Conclusion Clinical features of AOSD patients in the elderly were described in our cohort. Although the main clinical characteristics were similar comparing older and younger patients, patients aged over 60 years at disease onset were characterised by an increased prevalence of serositis, comorbidities, mostly cardiometabolic, and a higher mortality rate. Age predicted the presence of parenchymal lung disease and mortality, and it could be considered a negative prognostic factor in AOSD.

Objective To compare clinical features and treatments of patients with systemic JIA (sIJA) and adult-onset Still’s disease (AOSD). Methods The clinical charts of consecutive patients with sJIA by International League of Association of Rheumatology criteria or AOSD by Yamaguchi criteria were reviewed. Patients were seen at a large paediatric rheumatology referral centre or at 10 adult rheumatology academic centres. Data collected included clinical manifestations, inflammation biomarkers, systemic score, macrophage activation syndrome (MAS), parenchymal lung disease, disease course, disability, death and medications administered. Results A total of 166 patients (median age at diagnosis 5 years) with sJIA and 194 patients with AOSD (median age at diagnosis 41 years) were included. The frequency of fever, rash, arthralgia, abdominal pain, MAS, parenchymal lung disease and increased acute phase reactants and ferritin were comparable between the two cohorts. Patients with sJIA had a higher prevalence of arthritis, whereas patients with AOSD had experienced leucocytosis and extra-articular organ involvement more frequently. Patients with AOSD were given more commonly low-dose corticosteroids, whereas biologic DMARDs were administered first-line more frequently in patients with sJIA. Conclusion We found remarkable disparities in the prevalence of clinical manifestations between the two illnesses, which may partly depend on their classification by different criteria.

ObjectivesIgG4-related disease is a potentially systemic disease mimicking and overlapping with different autoimmune diseases, such as primary Sjögren’s syndrome (pSS). The involvement of salivary glands, previously called Mikulicz’s disease, has been reclassified as IgG4-related sialadenitis (SA). The aim of this study was to assess the prevalence of IgG4-SA in a cohort of Italian Caucasian patients presenting with xerostomia and to evaluate the eventual overlap between IgG4-SA and pSS.Material and methodsWe included 154 patients – 15 males and 139 females, mean age 54.18 ±14.24 years, who underwent minor salivary gland biopsy between March and December 2019 for xerostomia. Histopathology was evaluated using Chisholm-Mason (CM) and focus score (FS) for pSS and immunohistochemical study with IgG4 staining for IgG4-SA were performed. Serum autoantibodies (anti-SSa/RoAb, anti-SSB/LaAb, antinuclear antibodies, rheumatoid factor) were also assessed.ResultsIn 69 patients (44.8%) FS 0 was found, while FS ≥ 1 was presented in 85 (55.2%). Chisholm-Mason score < 3 and CM ≥ 3 was found in 73 (47.4%) and 81 (52.6%) cases, respectively. IgG4/high-power field level was 20 in 3 pSS patients (1.9%), but none of them had an IgG4/IgG ratio ≥ 40, as well as tissue fibrosis with storiform pattern, obliterative vasculitis, and tissue eosinophilia. The diagnosis of pSS, was confirmed in 92 patients (59.74%). No patient was definitively diagnosed with an IgG4-related disease.ConclusionsIn the case of xerostomia, the evaluation of the histopathological specimen for IgG4 should not be routinely performed, at least in an Italian-based Caucasian population. Moreover, immunohistochemistry should not be requested in the case of a negative result of biopsy for pSS.

Objectives To investigate survival of IL-1 inhibitors in monogenic autoinflammatory disorders (mAID) through drug retention rate (DRR) and identify potential predictive factors of drug survival from a real-life perspective. Patients and methods Multicentre retrospective study analysing patients affected by the most common mAID treated with anakinra or canakinumab. Survival curves were analysed with the Kaplan-Meier method. Statistical analysis included a Cox-proportional hazard model to detect factors responsible for drug discontinuation. Results Seventy-eight patients for a total of 102 treatment regimens were enrolled. The mean treatment duration was 29.59 months. The estimated DRR of IL-1 inhibitors at 12, 24 and 48 months of follow-up was 75.8%, 69.7% and 51.1%, respectively. Patients experiencing an adverse event had a significantly lower DRR (P=0.019). In contrast, no significant differences were observed between biologic-naïve patients and those previously treated with biologic drugs (P=0.985). Patients carrying high-penetrance mutations exhibited a significantly higher DRR compared with those with low-penetrance variants (P=0.015). Adverse events were the only variable associated with a higher hazard of treatment withdrawal [hazard ratio (HR) 2.573 (CI: 1.223, 5.411), P=0.013] on regression analysis. A significant glucorticoid-sparing effect was observed (P Conclusions IL-1 inhibitors display an excellent long-term effectiveness in terms of DRR, and their survival is not influenced by the biologic line of treatment. They display a favourable safety profile, which deserves, however, a close monitoring given its impact on treatment continuation. Special attention should be paid to molecular diagnosis and mutation penetrance, as patients carrying low-penetrance variants are more likely to interrupt treatment.

The objective of this study is to describe the possible prognostic impact of smoking habit on adult-onset Still’s disease (AOSD) patients, by the assessment of clinical characteristics, life-threatening complications occurrence, and mortality in smokers than non-smokers. A multicentre retrospective study of prospectively followed-up AOSD patients included in Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort was conducted. Out of 185 AOSD assessed patients, 45 smokers were identified. These showed a higher frequency of pericarditis (35.5% vs 16.4%, p = 0.011), pleuritis (33.3% vs 14.3%, p = 0.008), and abdominal pain (17.7% vs 6.4%, p = 0.035). Furthermore, smokers showed higher values of systemic score (6.4 ± 2.2 vs 5.4 ± 1.8, p = 0.004), an increased rate of macrophage activation syndrome (MAS) (28.9% vs 6.4%, p < 0.0001) and of parenchymal lung disease (17.7% vs 12.6%, p = 0.035). Although not significant, these patients more frequently experienced a poor prognosis (13.3% vs 4.3%, p = 0.074). Smoking habit predicted MAS occurrence in both univariate (HR: 5.98, 95% CI: 2.45–14.57, p < 0.0001) and multivariate regression models (HR: 6.21, 95% CI: 2.46–15.70, p < 0.0001). Smokers had a significant higher risk of parenchymal lung disease in both univariate (HR: 3.97, 95% CI: 1.43–11.02, p = 0.008) and multivariate regression models (HR: 3.90, 95% CI: 1.36–11.23, p = 0.012). Smoking habit also increased the risk of mortality in univariate regression model (HR: 4.25, 95% CI: 1.33–13.55, p = 0.015). Smoking habit resulted to be a negative prognostic factor on AOSD patients. Smokers were characterised by a higher frequency of serositis and higher values of systemic score. Additionally, these patients were more frequently burdened by MAS and parenchymal lung disease associated with a poor prognosis.Key points•Smoking habit resulted to be a negative prognostic factor on AOSD.•Smokers were characterised by an increased frequency of serositis and higher values of systemic score.•Cigarette exposure was associated with MAS and parenchymal lung disease in AOSD.

Chronic anterior uveitis is the most frequent among extra-articular manifestations of juvenile idiopathic arthritis (JIA) and a relevant cause of ocular morbidity in children. Asymmetric arthritis, early onset disease, female sex, and anti-nuclear antibody (ANA) positivity are counted among risk factors for developing this complication. It usually has insidious onset and asymptomatic chronic-relapsing course, but the persistence of low-grade chronic inflammation can lead to irreversible structural ocular damage and to vision-threatening complications. For such reasons, achieving a complete absence of inflammation through early targeted and aggressive treatments is a primary therapeutic goal in these patients. This review is aimed at summarizing scientific evidence about biologic rescue therapy of JIA-related uveitis in patients who fail to achieve clinical remission, in spite of being treated with conventional disease-modifying anti-rheumatic drugs (cDMARDs) and at least one biologic tumor necrosis factor (TNF)-α inhibitor. Interleukin (IL)-6 inhibition appears a promising and safe option for refractory JIA-related uveitis. Abatacept and rituximab proved to be beneficial as well, but their efficacy together with some safety concerns needs to be more extensively evaluated.

To evaluate the efficacy and safety of intravenous (iv) neridronate in patients affected by transient osteoporosis of the hip (TOH).We retrospectively evaluated the clinical records of patients affected by TOH treated with iv neridronate in our department. We treated patients with a value of visual analogue scale (VAS)-pain ≥ 80/100 mm at diagnosis, limited range of movement and magnetic resonance images (MRI) findings suggestive of TOH. The regimen used was: one iv infusion at day 0, 3, 6, 9 (100 mg for each infusion: total of 400 mg). This protocol was repeated in refractory cases. Recovery was defined as VAS-pain level ≤20/100. Concomitant use of analgesics was allowed. Paired Student t-test was used to assess VAS-pain change.Five patients were male, 3 were female. Mean age was 54.5±2.12 years old. Mean body mass index was 26.57±2.22. Mean time to diagnosis, since the onset of the symptoms, was 75±21.21 days. Mean number of neridronate infusions was 7.5±2.56. Mean time of recovery was 57±45.96 days. Mean VAS-pain at baseline was 84±2,24. Mean VAS-pain after treatment was significantly reduced (p0.001) with a value of 12.12±6.46. None of the patients needed analgesics after treatment. No adverse event was reported. In 5 cases, post-treatment MRI showed complete bone marrow oedema resolution.Intravenous neridronate is effective and safe in the treatment of TOH and its use may lead to a faster resolution of the disease.

Adult onset Still's disease (AOSD) is a rare systemic autoinflammatory disease, characterised by fever, arthritis, and skin rash, and joint involvement is one of its clinical manifestations. The aims of this work were to assess joint involvement, to describe main patterns of involvement, and associated clinical characteristics. In this work, we aimed at assessing the joint involvement in AOSD by using MRI, to describe main patterns and associated clinical characteristics. In addition, we aimed at assessing the global transcriptomic profile of synovial tissues in AOSD to elucidate possible pathogenic pathways involved. We also evaluated the global transcriptomic profile of synovial tissues to elucidate possible pathogenic pathways involved in the disease. Thus, AOSD patients, who underwent to MRI exam on joints, were assessed to describe patterns of joint involvement and associated clinical characteristics. Some synovial tissues were collected for RNA-sequencing purposes. The most common MRI finding was the presence of synovitis on 60.5%, mainly in peripheral affected joints, with low to intermediate signal intensity on T1-weighted images and intermediate to high signal intensity on T2-fat-saturated weighted and STIR images. Bone oedema and MRI-bone erosions were reported on 34.9% and 25.6% MRI exams, respectively. Patients with MRI-bone erosions showed a higher prevalence of splenomegaly, a more frequent chronic disease course, lower levels of erythrocyte sedimentation rate, and ferritin. In AOSD synovial tissues, a hyper-expression of interleukin (IL)-1, IL-6, and TNF pathways was shown together with ferritin genes. In conclusion, in AOSD patients, the most common MRI-finding was the presence of synovitis, characterised by intermediate to high signal intensity on T2-fat-saturated weighted and STIR images. MRI-bone erosions and bone oedema were also observed. In AOSD synovial tissues, IL-1, IL-6, and TNF pathways together with ferritin genes resulted to be hyper-expressed.

Objectives No clear-cut guidelines exist on the use of diagnostic procedures for idiopathic inflammatory myopathies (IIM) and only minimal and conflicting data report the use of ultrasound (US). In this regard, we aimed to assess if grey-scale (GS) and Power Doppler (PD) US, graded with a 0–3-point scale, may be a reliable tool in a cohort of patients affected by IIM. Methods All patients underwent US examination of both thighs in axial and longitudinal scans. Oedema and atrophy, both assessed in GS and PD, were graded with a 0–3-point scale. Spearman’s test was used to identify the correlations between US and clinical and serological variables. Results A total of 20 patients were included. Six and two patients were evaluated twice and three times, respectively. Muscle oedema was found to be directly correlated with physician global assessment (PhGA), serum myoglobin and PD and negatively with disease duration. PD score was positively correlated to PhGA and negatively to disease duration. Muscle atrophy directly correlated with Myositis Damage Index, disease duration and patient’s age. The single-thigh sub-analysis evidenced a direct correlation between PD score and Manual Muscle Test. Conclusions In our cohort, we found that oedema and PD are strictly related to early, active myositis, suggesting that an inflamed muscle should appear swollen, thickened and with Doppler signal. Conversely, muscle atrophy reflects the age of the patient and the overall severity of the disease. Such findings shed a new, promising, light on the role of US in diagnosis and monitoring of IIMs.

IntroductionOsteoporosis is the most common bone tissue disease and it is characterized by a re�duced bone mineral density (BMD). The main physiopathological mechanisms converge on the un�coupling between bone formation and resorption, thus leading to an enhanced risk of fractures. Several papers have documented the inverse relationships linking high inflammatory cytokines, anti�citrullinated protein antibodies, rheumatoid factor, and BMD in rheumatoid arthritis (RA). Rituximab (RTX) is a chimeric monoclonal antibody directed against the CD20 receptor of B cells. Since the Food and Drug Administration approved it for RA in 2006, there have been many clinical experiences regarding its use. Nevertheless, few studies evaluate the effect of rituximab on BMD. RA is a disease characterized by immune dysfunction with high levels of inflammatory cytokines, autoantibodies, and it is reasonable that a B cell depleting therapy could restore a physiological cytokine balance, thus exerting an osteoprotective effect on the bone tissue. The purpose of this paper is to highlight any difference in BMD and to assess differences in body composition over a retrospective 18-month follow-up period after RTX treatment with a B cell depleting therapy.Material and methodsWe analyzed by dual energy X-ray absorptiometry BMD expressed as g/cm2 and body composition modifications over 18 months with RTX treatment of 20 postmenopausal RA patients.ResultsAfter eighteen months of therapy with RTX, a statistically significant increase in vertebral (L1–L4) BMD and the stability of femoral BMD were documented.ConclusionsRituximab is associated with an improvement of vertebral and preservation of femo�ral BMD, suggesting a bone-sparing effect due to B cell depletion. Furthermore, patients displayed a redistribution of fat masses toward the hip region.

IntroductionSarcopenia is the pathological reduction of skeletal muscle mass and strength. This condition is often underestimated in clinical practice, particularly in connective tissue diseases. The purpose of this study is to evaluate the prevalence of low muscle mass in primary Sjögren’s syndrome (pSS) and to explore the relationships linking muscles and bone tissue.Material and methodsTwenty-eight postmenopausal pSS patients were matched with 30 healthy controls and their body composition analysis was performed by dual-energy X-ray absorptiometry to investigate for sarcopenia considering appendicular lean mass (ALM) and the skeletal muscle mass index (SMI) as references. Bone mineral density analysis of lumbar spine (L1–L4), whole femur, femoral neck and whole body was also performed. Linear regression was used to assess the relationship between body composition and bone mineralization.ResultsLow muscle mass was significantly higher in the pSS group compared to controls whether expressed as ALM, SMI [odds ratio (OR) = 18.40, confidence interval (CI): 4.84–72.08, p < 0.0001] or considering total body lean masses. Lean masses appeared to be the best estimators of bone mineralization: total lean body mass (TLBM) lumbar spine R2 = 0.72, p < 0.0001; TLBM femoral neck R2 = 0.36, p < 0.004; lean mass of upper limbs lumbar spine R2 = 0.70, p < 0.0001; femoral neck R2 = 0.66; lean mass of lower limbs lumbar spine R2 = 0.66, p < 0.0001; femoral neck R2 = 0.44, p = 0.008). Primary Sjögren’s syndrome patients had a significantly higher android/gynoid fat ratio compared to controls.ConclusionsFemale pSS patients have lower muscle mass compared to healthy controls and are exposed to a higher risk of developing sarcopenia than healthy subjects. Our research demonstrates that the amount of lean tissue is the main predictor of bone mineralization in pSS.

EULAR recommendations do not suggest which biologic disease-modifying anti-rheumatic drug (bDMARD) should be preferred after failure of a first bDMARD in the treatment of rheumatoid arthritis (RA). In particular, few data are available regarding the effectiveness of a second-line bDMARD after failure of abatacept (ABA), tocilizumab (TCZ), and rituximab (RTX). The aim of this study was to analyze the retention rate of a second line with tumor necrosis factor inhibitors (TNFi) or other mechanisms of action (MoAs), after the failure of either RTX, TCZ, or ABA.Two hundred and seventy-eight RA patients from the Italian GISEA registry were included in the study. RTX was the first bDMARD in 18% of patients, ABA in 45.7%, and TCZ in 36.3%, while the second bDMARD was a TNFi (group 1) in 129 patients and an agent with a different MoA (group 2) in 149.During a median follow-up of 22 months (IQR 68), 129 patients discontinued their treatment; patients of group 1 discontinued the treatment more frequently than patients of group 2 (p0.001) with retention rates of 33.6±5.7% and 63.6±4.6% after 104 weeks for group 1 and group 2, respectively (p0.001). At multivariate analysis, the mechanism of action was the only predictor for the maintenance in therapy.According to our data, ABA, RTX, and TCZ seem to maintain a good retention rate also when used as a second-line therapy, suggesting their use after the failure of a non-TNFi as first-line therapy. However, specifically designed studies are needed to evaluate the more appropriate therapeutic strategies in RA, according to the first-line drug, including new targeted synthetic DMARDs. Key Points • A large proportion of rheumatoid arthritis patients fail the first biologic DMARD. • Few data are available about the efficacy of biologic DMARD after the failure of a non-TNF inhibitor. • Abatacept, rituximab, or tocilizumab seem to maintain a good retention rate after the failure of a first-course therapy with a non-TNF inhibitor.

Not available

Aims: Switching from originator to biosimilar is part of current practice in inflammatory rheumatic musculoskeletal diseases (iRMDs) such as rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondylarthritis (axSpA), with evidences derived from both etanercept (ETN) to SB4-switching randomized controlled trials and real-life registries. We investigated the safety and treatment persistence of ETN/SB4 in a multi-iRMD cohort derived from two rheumatology departments in our region. Methods: Adult patients with iRMDs, treated with ETN for at least 6 months and switched to SB4 in stable clinical condition, were eligible for this retrospective evaluation. Retrospective data on adverse events, loss of efficacy and persistence on treatment were collected until latest available follow-up. Results: A total of 220 patients (85 RA, 81 PsA, 33 axSpA, 14 juvenile idiopathic arthritis and seven other conditions; 142 females, mean age 58 ± 7 years, disease duration 12 ± 4 years, ETN duration 7 ± 4 years) were enrolled, with median follow-up of 12.1 (9.7–15.8) months. A total of 50 patients (22.7%) presented with at least one adverse event, with 36 (16.4%) disease flares and 30 (13.6%: 11 for safety and 19 loss of efficacy) SB4 withdrawals. Cumulative SB4 treatment persistence was 99.1%, 88.6% and 64.6% at 6, 12 and 18 months respectively. Back-switch to ETN was performed in 17/30 cases, the remaining cases were managed with change of biologic disease modifying or conventional synthetic anti-rheumatic drug. Age was the only significant predictor of SB4 interruption at 6 months. Conclusion: Our real-life data confirm the safety profile of switching from ETN to SB4, with slightly higher treatment persistence rates compared with other real-life registries.

We read with interest the article by Ramiro et al 1 about a cohort of patients affected by severe COVID-19 pneumonia. The authors evidenced the efficacy of 5 days of methylprednisolone (MP) (a single bolus of 250 mg, followed by 80 mg on days 2–5) plus, in case of insufficient response, tocilizumab (TCZ) 8 mg/kg, in reducing mortality and preventing invasive ventilation (IV). As the massive lung damage during COVID-19 pneumonia is thought to be caused by an aberrant inflammatory response mediated by a massive release of inflammatory cytokines and chemokines, the use of biological immunosuppressants has been widely proposed. The rationale supporting their use is not only an antiviral effect,2 but the selective anti-inflammatory role and the capability of interrupting the cytokine cascade eventually responsible for lung failure. TCZ, a monoclonal antibody directed against interleukin 6 (IL-6) receptor, was the first biological drug administered in a Chinese cohort of patients. Despite preliminary promising data, recent reviews and meta-analysis did not find statistically significant differences, in terms of mortality, intensive care unit (ICU) admission and requiring of IV, between patients treated with TCZ and …

Objectives Microcrystal-induced arthritis is still an unresolved paradigm for medicine. Overt inflammation may be absent even when crystals occur in SF. Recently, the production of neutrophil extracellular traps (NETs) embedding MSU crystals has been proposed as a possible mechanism of the auto-resolution of the inflammatory phase during gout. We aimed to verify and quantify the release of NETs in SFs during gout and pseudogout attacks and to compare any differences with respect to crystals and neutrophils number, and to analyse activation of necroptosis pathway in SF from crystal-induced arthritis. Methods SF samples were obtained by arthrocentesis from 22 patients presenting acute crystal-induced arthritis, gout or pseudogout (n = 11 each group), and from 10 patients with acute non-crystal arthritis as controls. NETosis was quantified in SF by nucleic acid stain and by quantification of human neutrophil elastase. Activation of phosphorylated MLKL was assessed by western blot. Results We observed that SF neutrophils encountering MSU and CPPD crystals during episodes of gout and pseudogout release NETs in relation to the number of crystals in SF and irrespective of neutrophil density and type of crystal. This release was accompanied by necroptosis through the activation of the MLKL pathway. Conclusions Our findings suggest that a role of NETs in crystal-induced arthritis is to ‘trap extracellular particles’, including microcrystals. Embedding crystals in aggregates of NETs may be the basis of tophi and CPPD deposition, and may have implications for disease evolution rather than for spontaneous resolution of the acute attack.

Objectives The objectives of this study were to study with Power Doppler US (PDUS) the SI joints (SIJs) of patients with suspected active sacroiliitis, to describe SIJ flows with spectral wave analysis (SWA) on Doppler US, and to correlate US data with both clinical characteristics and presence of SIJ bone marrow oedema (BME) in subsequent MRI. Methods A total of 42 patients (32 females and 10 males, mean age 46.8 years) with recent onset of inflammatory back pain (IBP) were included. Every patient underwent US examination with a convex 1–8 MHz probe [scoring PDUS signals with a three-point scale and describing flows in SWA calculating the mean Resistive Index (RI)] and subsequent MRI of the SIJs. Results PDUS signals were detected in 34 patients and 62 SIJs. In 29 patients and 56 SIJs, MRI revealed BME. A definite diagnosis of SpA was made in 32 patients. PDUS signals were more frequent (P Conclusions PDUS and SWA of SIJs demonstrate good diagnostic accuracy for active sacroiliitis compared with MRI.

We read with interest the article by Monti et al ,1 who evidenced, in a cohort of subjects affected by COVID-19, a low prevalence of patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs). Despite a notable heterogeneity in different countries and even in different regions of the same country, a high lethality is reported among elderly patients with several comorbidities.2 National and international registers have been created to collect patients affected by rheumatic diseases, as well as patients with interstitial lung disorders.3 Since 20 February to 7 April 2020, we collected clinical data of 859 patients affected by different rheumatic diseases and sarcoidosis, treated with stable and full dosage of bDMARDs or tsDMARDs at Siena Rheumatology Unit and Siena Regional Referral Centre for Sarcoidosis. All patients underwent a telephone survey in order to establish their clinical status, the appearance of signs and symptoms of COVID-19 and the presence of …

The letter of Monti et al 1 on covid-19 in patients with chronic arthritis treated with immunosuppressive therapies stimulates some considerations. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects cells through the ACE-2 receptor, which is highly expressed in both the lung and the heart. Besides direct tissue injury, SARS-CoV-2 infection can also induce an exaggerated host immune response, frequently inducing a cytokine release syndrome contributing to multiorgan dysfunction. Indeed, high levels of circulating cytokines, particularly interleukin (IL)-6, IL-1β and tumour necrosis factor-alpha (TNFα), are commonly found in patients with covid-19, correlating with mortality (IL-6).2 Current therapeutic strategy involves agents counteracting viral invasion and replication, and inhibitors of cytokine-sustained inflammatory reactions. Indeed, different cytokines involved in the acute inflammatory response are currently targeted by specific medications otherwise employed in the treatment of rheumatic diseases. Agents inhibiting the activity of IL-1β, TNFα, IL-6 and the Janus Kinase 1 and 2 (JAK 1/2)-Signal Transducer and Activator of Transcription (STAT) pathway are currently under consideration in the treatment of covid-19-associated respiratory syndrome.3 We are here providing some arguments to help achieve a more rational therapeutic decision. In any case, as a general consideration, the short-term period of administration of these agents is …

This paper is aimed at investigating whether peripheral dysfunction at the neuromuscular level may represent a pain generator in fibromyalgia. We studied the prevalence of spasmophilia (SP), carpal tunnel syndrome (CTS) and ulnar neuropathy at the elbow (UNE) in a group of 40 subjects suffering from fibromyalgia. Clinical and electrophysiological data were obtained to ascertain whether comorbid conditions were present. For subjective evaluation of symptoms severity, validated questionnaires for CTS and UNE were completed by patients. Twenty subjects were positive for SP (50%); CTS was diagnosed in 12 subjects (30%); no patient suffered from UNE; 6 subjects were affected at the same time by SP and CTS (15%); 14 subjects (35%) were affected by SP alone. The prevalence of CTS and SP was higher in fibromyalgia subjects than in the general population. The scores of the questionnaires related to CTS were significantly higher in fibromyalgia subjects positive for CTS, with respect to the other subjects. In fibromyalgia, CTS and SP may be considered clinical entities in themselves, the importance of which lies in their acting as peripheral pain generators that enhance or initiate central sensitization, thereby contributing to chronic widespread pain. The amplification of pain is indeed a correctable/misguided message that occurs inside the brain of fibromyalgia subjects and identification and local treatment of pain generators would lessen the total pain burden. The magnitude of the overlap in symptoms between fibromyalgia and CTS/SP necessitates careful investigation of these conditions.

Objective To establish clinical consensus for the optimal placement of TNF inhibitor (TNFi) in DMARDs-naive RA patients. Methods The steering group was composed of 15 Italian rheumatologists expert in the field of RA, who proposed and selected by consensus the clinically relevant questions on the role of TNFi treatment in DMARDs-naive RA patients. The question was rephrased according to the population, intervention, comparison and outcome statement. The available scientific evidence on this topic were collected by updating the systematic literature reviews used for the EULAR 2013 recommendations up to January 2016. The aspects evaluated in the studies concerned clinical efficacy, radiographic structural damage and safety. After the systematic literature review the expert panel formulated a consensus statement, and a modified Delphi panel evaluated the level of agreement between panellists (strength of recommendation). Results From a total of 1080 records we have included 6 studies, 2 randomized clinical trials and 4 open-label extension trials. Evidence from publications generated three statements for the final consensus document. The systematic literature review and the consensus statements developed showed that, for patients with early RA and in the presence of a treat-to-target strategy, the immediate use of anti-TNFi compared with an early (within 12 weeks) step-up to anti-TNF therapy did not confer a significant advantage regarding clinical, functional and radiographic outcomes. Conclusion The most appropriate placement of the TNFi therapy in the treatment algorithm of early RA still remains a challenging clinical question that needs to be further addressed.

OBJECTIVE Since Behcet's syndrome (BS) is the prototype of inflammation-induced thrombosis, immunosuppressants are recommended in place of anticoagulants. We undertook this study to assess the clinical efficacy and the corticosteroid-sparing effect of adalimumab (ADA)-based treatment versus disease-modifying antirheumatic drug (DMARD) therapy in a large retrospective cohort of patients with BS-related venous thrombosis. METHODS We retrospectively collected data on 70 BS patients treated with DMARDs or ADA-based regimens (ADA with or without DMARDs) because of venous complications. Clinical and imaging evaluations were performed to define vascular response. We explored differences in outcomes between ADA-based regimens and DMARDs with respect to efficacy, corticosteroid-sparing role, and time on treatment. We also evaluated the role of anticoagulants as concomitant treatment. RESULTS After a mean ± SD follow-up period of 25.7 ± 23.2 months, ADA-based regimens induced clinical and imaging improvement of venous thrombosis more frequently (P = 0.001) and rapidly (P < 0.0001) than did DMARDs. The mean dose of corticosteroids administered at the last follow-up visit was significantly lower with ADA-based regimens than with DMARDs (P < 0.0001). The time on treatment was significantly longer with ADA plus DMARDs than with DMARDs alone (P = 0.002). No differences were found in terms of efficacy and time on treatment between DMARDs or ADA-based regimens among patients who received anticoagulants and those who did not. CONCLUSION In this large retrospective study, we have shown that ADA-based regimens are more effective and rapid than DMARDs in inducing resolution of venous thrombosis in BS patients, allowing reduction of steroid exposure. Moreover, our findings suggest that anticoagulation does not modify the efficacy of either ADA-based regimens or DMARDs for venous complications.

The aim of the present study was to compare long-term adalimumab (ADA) and infliximab (IFX) retention rates in patients with intermediate, posterior, or panuveitis. Additional aims are as follows: (i) to identify any difference in the causes of treatment discontinuation between patients treated with ADA and IFX; (ii) to assess any impact of demographic features, concomitant treatments, and different lines of biologic therapy on ADA and IFX retention rates; and (iii) to identify any correlation between ADA and IFX treatment duration and the age at uveitis onset, the age at onset of the associated systemic diseases, and the age at the start of treatment. Clinical, therapeutic, and demographic data from patients with non-infectious intermediate, posterior, or panuveitis treated with ADA or IFX were retrospectively collected. Kaplan-Meier plot and log-rank (Mantel-Cox) test were used to assess survival curves. One hundred eight patients (188 eyes) were enrolled; in 87 (80.6%) patients, uveitis was associated with a systemic disease. ADA and IFX were administered in 62 and 46 patients, respectively. No statistically significant differences were identified between ADA and IFX retention rates (p value = 0.22). Similarly, no differences were identified between ADA and IFX retention rates in relation to gender (p value = 0.61 for males, p value = 0.09 for females), monotherapy (p value = 0.08), combination therapy with conventional disease-modifying antirheumatic drugs (log-rank p value = 0.63), and different lines of biologic therapy (p value = 0.79 for biologic-naïve patients; p value = 0.81 for subjects previously treated with other biologics). In conclusion, ADA and IFX have similar long-term retention rates in patients with non-infectious intermediate, posterior, and panuveitis. Demographic, clinical, and therapeutic features do not affect their long-term effectiveness.

Background: No data on the permanent and curative effect of bisphosphonate treatment in patients with complex regional pain syndrome type-1 (CRPS-1) are currently available. The aim of this pre-specified, open-label, observational study was to evaluate the long-term efficacy and safety of neridronate treatment. Design: A pre-specified, open-label, extension study. Methods: Patients treated with intramuscular (IM) placebo in the double-blind phase of the study were assigned to 100 mg intravenous (IV) neridronate treatment administered 4 times over 10 days. These patients, together with those previously treated with 400 mg IM neridronate, were followed for 1 year. Efficacy was assessed using a visual analogue scale (VAS) pain score. Changes in clinical signs and symptoms, quality of life (QoL) using the Short Form Health Survey (SF-36), and the McGill Pain Questionnaire were also assessed. Results: Benefits on pain, clinical and functional measures were maintained and further improved over 12 months in most patients treated with neridronate administered either IM or IV. In IM-treated patients, the percentage of those defined as responders (VAS score reduction ≥ 50%) progressively increased up to day 360 to 32 of 35 patients (91.4%). Among the 27 patients referred to as responders at the end of the double-blind phase, 26 reported the same result at day 360 (96.3%). In IV-treated patients, a responder rate of 88% (22 out 25) was found at day 360 (p = 0.66 between groups). Consistent improvements were also observed for all clinical signs and functional questionnaire. No drug-related adverse events were reported during the study. Conclusion: In patients with acute CRPS-1, the benefit in pain, clinical, and functional measures observed a few weeks after neridronate treatment administered either IM or IV is maintained and further improved over 12 months. Parenteral neridronate induces permanent disease remission preventing chronic pain and motor dysfunction. Trial registration: EU Clinical Trials Register (EudraCT Number): 2014-001156-28

Background:Previous studies have compared Patient-Reported Outcomes (PROs) in Spondyloarthritis (SpA); a recent one has found similarity in Psoriatic Arthritis (PsA) and axial patients1.Objectives:To describe PROs at SpA diagnosis (new or confirmed), by type of SpA and by gender.Methods:SIRENA is an Italian, prospective Registry of SpA patients diagnosed according to ASAS criteria and naïve to any DMARDs. At inclusion, patients were classified as predominant axial (AxSpA) or mainly peripheral (pSpA). PROs showed in the Table 1 were collected and analysed descriptively.Table 1.PhGA and PROs at diagnosis*AxSpA*pSpAAll(n=123)Women(n=64)Men(n=58)All(n=227)Women(n=109)Men(n=118)PhGA, n1156054222105117mean (SD)50.2 (28.6)54.8 (26.7)45.0 (30.1)45.4 (25.9)49.9 (25.6)41.3 (25.6)median (min, max)52.0 (0-100)62.0 (0-100)43.5 (0-100)48.5 (0-100)50.0 (1.0-100)40.0 (0-95.0)PtGA, n1125952209102107mean (SD)56.4 (27.8)61.5 (25.8)50.3 (29.2)50.3 (26.2)56.4 (23.1)44.5 (27.7)median (min, max)63.0 (0-100)70.0 (2.0-100)50.0 (0-100)50.0 (0-100)58.5 (7.0-100)47.0 (0-100)Pain VAS score, n1136052207101106mean (SD)56.7 (28.3)61.1 (26.6)50.6 (29.1)51.9 (26.8)57.4 (25.3)46.8 (27.3)median (min, max)60.0 (0-100)69.5 (2.0-100)50.0 (0-100)53.0 (0-100)61.0 (0-100)48.5 (0-100)Sleep VAS score, n1136052211103108mean (SD)55.3 (29.3)57.4 (29.5)52.3 (29.2)44.0 (30.1)50.4 (29.8)37.9 (29.2)median (min, max)59.0 (0-100)61.5 (0-100)53.0 (0-100)44.0 (0-100)53.0 (0-100)34.0 (0-100)BASFI, n11058511336568mean (SD)4.6 (2.8)5.2 (2.6)3.9 (2.8)3.5 (2.6)4.0 (2.6)3.1 (2.4)median (min, max)5.1 (0-9.7)5.8 (0-9.4)3.6 (0-9.6)2.9 (0-10.0)3.9 (0-10.0)2.45 (0-8.9)BASDAI, n11259521397069mean (SD)5.2 (2.4)5.8 (2.3)4.5 (2.3)5.2 (2.3)5.8 (2.1)4.6 (2.3)median (min, max)5.5 (0-9.3)6.2 (0-9.3)4.5 (0.3-9.2)5.5 (0.2-10.0)6.1 (1.0-10.0)4.8 (0.2-9.2)HAQ-DI score, n109585020399104mean (SD)0.9 (0.7)1.1 (0.7)0.6 (0.6)0.7 (0.7)0.9 (0.7)0.6 (0.6)median (min, max)0.8 (0.0-2.5)1.1 (0-2.5)0.5 (0-2.3)0.6 (0.0-2.8)0.8 (0-2.8)0.4 (0-2.6)WPAI% work time missed, n4919301074562mean (SD)7.3 (21.4)4.2 (9.5)9.2 (26.3)8.8 (24.7)8.6 (25.6)8.9 (24.3)median (min, max)0 (0-100)0 (0-35.1)0 (0-100)0 (0-100)0 (0-100)0 (0-100)% impairment at work, n6733341346173mean (SD)48.2 (31.9)58.5 (26.6)38.2 (33.7)39.7 (31.4)45.4 (30.9)34.9 (31.2)median (min, max)50.0 (0-100)60.0 (0-100)25.0 (0-100)40.0 (0-100)50.0 (0-100)30.0 (0-100)% overall work impairment, n4819291064561mean (SD)44.1 (33.0)52.4 (27.9)38.7 (35.3)40.1 (33.0)45.1 (33.1)36.4 (32.7)median (min, max)45.0 (0-100)60.0 (0-100)20.0 (0-100)40.0 (0-100)50.0 (0-100)30.0 (0-100)% activity impairment, n10053461839390mean (SD)56.7 (28.6)63.4 (23.9)48.0 (31.0)48.5 (30.3)55.3 (28.7)41.4 (30.4)median (min, max)60.0 (0-100)70.0 (0-100)50.0 (0-100)50.0 (0-100)60.0 (0-100)40.0 (0-100)* The sum does not add up to the total because of some missing values.Results:From 23 sites, 123 AxSpA and 227 pSpA patients were analysed. Diagnosis was new in 58% of AxSpA and 77% of pSpA. 85.5% of the pSpA had PsA, while in AxSpA the most frequent type was Ankylosing Spondylitis (48.8%). Time from symptom onset to diagnosis was higher in AxSpA than in pSpA (median 36 vs 24 months, respectively). At inclusion, composite disease activity measures showed high disease activity for AxSpA (mean ASDAS-CRP 3.1) and moderate disease activity for pSpA (mean DAS28 3.6; mean DAPSA 22.5). AxSpA patients had numerically worse values than pSpA in all the PROs collected, except for BASDAI score that was similar (mean 5.2). For both AxSpA and pSpA, all PROs were worse in women than men, except for the % of work time missed. PtGA scores were higher than PhGA, in each group and gender.Conclusion:At diagnosis, SpA patients perceive a slightly higher disease burden than assessed by Physicians. For PROs other than BASDAI, AxSpA reported a worse impact than pSpA. Overall, women showed a higher disease impact than men.References:[1]Michelsen B. et al. PLoS ONE 2015; 10(4): e0123582.Disclosure of Interests:Rosario Foti Speakers bureau: Speaker bureau honoraria from Eli Lilly, Sanofi, MSD, Janssen, AbbVie, Bristol-Myers Squibb, Celgene, Roche, Consultant of: Consultancy fees from Eli Lilly, Sanofi, MSD, Janssen, AbbVie, BMS, Celgene, Roche, Gabriella Cardinale: None declared., Luisa Costa: None declared., Franco Franceschini: None declared., Francesco Ciccia Speakers bureau: Speaker bureau honoraria from AbbVie, Abiogen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Pfizer, Novartis, Roche, Consultant of: Consultancy fees from Novartis, Pfizer, Janssen, Eli Lilly, Roche, Celgene, Grant/research support from: Grant/research support from Pfizer, Novartis, Celgene, Janssen, Roche, Antonio Marchesoni: None declared., Giuliana Guggino Speakers bureau: Speaker bureau honoraria from Celgene, Sandoz, Pfizer, Grant/research support from: Grant/research support from Pfizer, Celgene, Maurizio Rossini: None declared., Ennio Lubrano Di Scorpaniello: None declared., Bruno Frediani: None declared., Maria Sole Chimenti: None declared., Gerolamo Bianchi: None declared., Giuseppe Galfo: None declared., Silvia Marelli Employee of: Employee of Janssen-Cilag SpA Italy, Ennio Favalli Speakers bureau: Consulting fees and/or speaking engagements from AbbVie, Bristol-Myers Squibb, Lilly, Merck Sharp & Dohme, Pfizer, Galapagos, Sanofi-Genzyme, and UCB.

ObjectivesPolymyalgia rheumatica (PMR) is the commonest inflammatory disorder of the elderly; an association with environmental triggers and a deregulated immune response have been described. The aim of this study was to investigate the association of environmental triggers before the onset of PMR.Material and methodsThe database of 58 consecutive PMR patients recruited from a single rheumatology secondary care setting was retrospectively analyzed to investigate the frequency of environmental triggers and correlations with clinical characteristics, ultrasound and laboratory data.ResultsFifteen PMR patients (26%) described a connection with environmental agents: six PMR patients reported a vaccination, 4 reported a respiratory tract infection, 5 reported seasonal influenza before the onset of the disease. The model of multivariate linear regression which better predicted a shorter time to normalize inflammatory reactants (R2 = 27.46%, p = 0.0042) comprised the presence of an environmental trigger and a higher PCR. A linear regression analysis confirmed an inverse correlation between PCR at onset and time to normalize inflammatory reactant (r = –0.3031, p = 0.0208). A significant correlation was demonstrated between presence of environmental trigger and shorter time to normalize inflammation (r = –0.5215, p < 0.0001), and lesser frequency of gleno-humeral synovitis on US (r = –0.3774, p = 0.0038).ConclusionsOur work describes a correlation between environmental triggers in PMR and higher CRP at diagnosis, faster response to therapy, and milder shoulder synovitis. We may suppose that these patients belong to a more specific subtype of PMR, in whom external stimuli, such as vaccination or infection, may lead to a deregulated response within the context of an impaired senescent immuno-endocrine system.

Rituximab is a human/murine chimeric anti-CD20 monoclonal antibody. It is largely used to treat B cell malignancies and has become standard in the management of B cell‑mediated diseases such as rheumatoid arthritis and granulomatosis with polyangitis. The effects of rituximab need to be monitored by B cell phenotyping. Evaluate possible surface markers for monitoring B cell development in response to rituximab treatment. This review discusses the literature on the B cell surface markers analysed by flow cytometry in patients treated with rituximab. A panel of biomarkers of response to treatment to monitor by flow cytometry is also suggested. B cell phenotyping is useful to predict clinical relapses after rituximab treatment. The proposed panel of biomarkers includes CD38++CD24++IgD+/- immature B cells and IgD-CD38+/- memory B cells. In responders, Th1/Th2 balance and tolerance cells (CD4+CD25+CD127-/low Treg cells and CD19+CD24hiCD38hi Breg cells) tend to be restored after rituximab therapy. Furthermore, in responder patients, indirect depletion of CD19+/-CD27++CD38++ preplasma cells can be proposed as a predictor of response. Flow cytometric analysis of samples from patients treated with rituximab is a useful strategy to stratify patients according to response to treatment. Identification of B cell differentiation stages by means of a specific flow cytometry panel could improve monitoring of rituximab effects and enable non-responders to be distinguished from good responders.