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ObjectiveTo investigate the associations between the Patient Global Assessment (PGA) and measures of disease activity in patients with rheumatoid arthritis (RA) in relation to disease duration and autoantibody status.Methods1412 patients from three independent cohorts were studied: a prospective cohort of 810 patients with early RA followed up for 24 months; a cross-sectional cohort of 210 patients with established RA in low disease activity; a cross-sectional cohort of 401 patients with established RA in moderate-to-high disease activity. Correlations of the PGA were analysed by Pearson’s coefficients and multivariable linear regression at baseline and at months 6, 12 and 24 in the overall populations and after stratification for autoantibody subgroup and remission status (Boolean remission, PGA near remission and non-remission).ResultsIn patients with early RA in non-remission, swollen joints correlated independently with the PGA; the correlation became progressively weaker but persisted at all time points in autoantibody-positive patients (adjusted r=0.30–0.12) but lost significance after month 12 in autoantibody-negative patients. Swollen joints independently correlated with the PGA also in near remission until month 12 (adjusted r=0.18–0.16) in autoantibody-positive patients. No independent correlations of inflammatory variables were instead found in patients with established RA irrespective of disease activity and autoantibody status.ConclusionsIn the early phases of RA, particularly in autoantibody-positive patients, inflammatory variables directly correlate with the PGA across different disease activity states. The optimal cut-off values of the PGA capable of identifying absence of disease should be better explored in relation to disease duration and autoantibody status.

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

Strategies aimed at expediting immunisation campaigns against COVID-19 include providing single vaccine doses to individuals with previous exposure to SARS-CoV-2 and delaying second doses. While such approaches are effective at the population level, immunogenicity yielded by one dose of vaccines in immunocompromised patients may be alarmingly low.1 2 Biological (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) interfere with the immune system at multiple levels and may variably reduce response to viral vaccines.3 Limited data on small numbers of rheumatic patients with variable diagnoses and treatments hamper definitive conclusions on the possible impact of immune-mediated inflammatory diseases, immunomodulatory drugs or both on the efficacy of the new generation of mRNA vaccines.4 5 Here we present interim data analysis on the immunogenicity of the BNT162b2 COVID-19 vaccine in 140 patients with chronic inflammatory arthritis all treated with b/tsDMARDs at the Division of Rheumatology of the IRCCS Policlinico San Matteo University Hospital of Pavia, receiving the first dose of vaccine between 24 and 31 March 2021. Patients were advised to discontinue both the b/tsDMARD and concomitant methotrexate around vaccination. In particular, the following suggestions were made: (1) for all the bDMARDs and methotrexate, withholding of therapy in the 7 days before and after vaccination; and (2) for tsDMARDs, withholding of therapy from the day before until day 7 after vaccination. For glucocorticoids and conventional synthetic DMARDs other than methotrexate, no modifications were advised. Blood samples were obtained immediately before vaccination and at day 21 after the first dose. Serum samples were tested using chemiluminescent immunoassay (LIAISON SARS-CoV-2 S1/S2 IgG; DiaSorin) for the quantitative characterisation of SARS-CoV-2 anti-S1 and anti-S2 IgG antibodies, with values >15 AU/mL indicating a positive result. Demographic and clinical variables were retrieved from the last available rheumatological assessment (median (IQR) 14 (5–19) days before vaccination) …

Purpose of review Vitamin D exerts extraskeletal functions, including immunomodulatory activity, protection against respiratory tract infections and pleiotropic effects on the cardiovascular system. Since the outbreak of the coronavirus disease-2019 (COVID-19) pandemic, several articles have suggested the potential involvement of vitamin D in reducing the risk and severity of the disease. Recent findings Epidemiological and observational studies support the hypothesis of a protective role of vitamin D but most studies are retrospective or based on small samples. However, the pandemic progression and the increased knowledge on the pathogenesis of COVID-19 have challenged the first evidence, suggesting also potential negative consequences derived by adequate vitamin D status. A cautious interpretation of the significance of low vitamin D25OH levels is advisable. The balance between over-activation of innate immunity and the exhaustibility of the adaptive immune response still needs to be clarified. In addition, the modulation of endothelial function, the down-regulation of renin, angiotensin-converting-enzyme (ACE) and angiotensin genes and the up-regulation of ACE2 expression is still an area of research. Summary Speculative hypotheses and observational data have suggested a protective role of vitamin D in COVID-19. However, many unanswered questions remain, aberrant detrimental effects of adequate vitamin D25OH levels cannot be excluded and whether its adequacy may prevent the infection or improve clinical outcomes needs to be assessed by adequately sized and designed population-based studies and intervention trials.

The safety of COVID-19 vaccination in rheumatic patients treated with biological (b) and targeted synthetic (ts) disease-modifying anti-rheumatic drugs (DMARDs) remains poorly explored.Reactogenicity, safety and disease flares following each of the two doses of the BNT162b2 mRNA vaccine was evaluated in 186 patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis treated with b/tsDMARDs, who discontinued anti-rheumatic treatments around vaccination. A group of 53 healthy controls was used for comparison.The frequency and severity of systemic events was similar to that reported in the general population, and no particular safety concerns emerged. The use of methotrexate reduced systemic reactogenicity (adjORs [95% CI] 0.49 [0.25-0.94] and 0.63 [0.32-0.99] after each vaccine dose), whilst no specific effects of different b/tsDMARDs were seen. Flares around vaccination were reported by 24.5% of the patients. Factors associated with flares were active disease (adjORs [95% CI] 2.8 [1.01-8.09] and 1.86 [0.99-6.03] after each vaccine dose) and use of JAKi (adjORs [95% CI] 3.96 [1.39-11.27] and 3.10 [0.99-7.85]). The percentage of cases requiring change or increase in DMARD therapy due to persistent worsening of disease activity at follow-up visits was low (3.2%).The safety of mRNA COVID-19 vaccination in arthritis patients on treatment with b/tsDMARDs is reassuring. In a regimen of peri-vaccine drug interruption, transient flares of the disease more commonly occur in association with active arthritis and use of shorter half-life drugs. Most flares do not require treatment escalation or change.

© Copyright Clinical and Experimental Rheumatology 2022., Objectives: To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies. Methods: We conducted a multicentre, international, retrospective cohort study. Results: 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD. Conclusions: The clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern.

Objectives To multidimensionally characterize macrophage activation syndrome (MAS) complicating adult-onset Still’s disease (AOSD) considering cytokine profile, inflammatory markers and multi-visceral involvement of the disease. To perform a high-dimensional phenotypic analysis of circulating immune cells in AOSD patients with and without MAS. To assess interferon (IFN)-related pathways in AOSD synovial tissues by a bulky RNA sequencing. Methods Clinical and biologic data were collected and compared in AOSD patients with and without MAS. Sera biomolecules were analysed by Luminex multiplexing technology. Mass cytometry (CyTOF) was used to characterize circulating immune cells. A bulky RNA sequencing was performed in AOSD synovial tissues. Results Forty consecutive AOSD patients were assessed, 14 complicated with MAS. Paralleling with increases of systemic score and ferritin, MAS patients showed higher levels of IL-1α, IL-1β, IL-1Ra, IL-2Ra, IL-6, IL-10, IL-17A, IFN-γ, G-CSF, MCP-1, MIP-1α and SCF. Combining the discriminatory ability of these data in identifying MAS, the best model was composed by systemic score, ferritin, IFN-γ and IL-10. By CyTOF analysis, MAS patients showed an increase of circulating ‘classical monocytes’ and a reduction of total NK cells. Our assessment showed 3477 IFN-related genes (IRGs) were differently expressed in AOSD synovial tissues. Conclusions A multidimensional characterization of AOSD patients suggested that IFN-γ, IL-10, ferritin and systemic score discriminated the occurrence of cytokine storm syndrome associated with MAS. The inflammatory milieu of AOSD and MAS may be related to a signature of circulating immune cells. Finally, our results about IRGs reinforced the role of IFN-γ in these 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.

The identification of anti-NXP2 antibodies is considered a serological marker of dermatomyositis (DM), with calcinosis, severe myositis and, in some reports, with cancer. Historically, these associations with anti-NXP2 antibodies have been detected by immunoprecipitation (IP), but in the last few years commercial immunoblotting assays have been released. The aim of this collaborative project was to analyse the clinical features associated to anti-NXP2 antibodies, both with commercial line blot (LB) and IP. Myositis-specific and myositis-associated autoantibodies were detected in single centres by commercial line blot (LB); available sera were evaluated in a single centre by protein and RNA immunoprecipitation (IP), and IP-Western blot. Sixty patients anti-NXP2+ (NXP2+) positive by LB were compared with 211 patients anti-NXP2 negative with idiopathic inflammatory myositis (IIM). NXP2+ showed a younger age at IIM onset (p = 0.0014), more frequent diagnosis of dermatomyositis (p = 0.026) and inclusion-body myositis (p = 0.009), and lower rate of anti-synthetase syndrome (p

Bone mineral density (BMD) reduction and fragility fractures still represent a major source of morbidity in rheumatoid arthritis (RA) patients, despite adequate control of the disease. An increasing number of clinical and experimental evidence supports the role of autoantibodies, especially anti-citrullinated protein antibodies (ACPAs), in causing localized and generalised bone loss in ways that are both dependent on and independent of inflammation and disease activity. The human receptor activator of nuclear factor kappa B and its ligand—the so-called RANK-RANKL pathway—is known to play a key role in promoting osteoclasts’ activation and bone depletion, and RANKL levels were shown to be higher in ACPA-positive early untreated RA patients. Thus, ACPA-positivity can be considered a specific risk factor for systemic and periarticular bone loss. Through the inhibition of the RANK-RANKL system, denosumab is the only antiresorptive drug currently available that exhibits both a systemic anti-osteoporotic activity and a disease-modifying effect when combined with conventional synthetic or biologic disease-modifying anti-rheumatic drugs (DMARDs). Thus, the combination of DMARD and anti-RANKL therapy could be beneficial in the prevention of fragility fractures and structural damage in the subset of RA patients at risk of radiographic progression, as in the presence of ACPAs.

Background & Aims Great interest has been raised by the possible protective role of vitamin D in coronavirus disease 2019 (COVID-19), but objective data on 25(OH)vitamin D deficiency in hospitalized COVID-19 patients are not conclusive. The aim of this study was to determine the prevalence of 25(OH)vitamin D deficiency in COVID-19 patients admitted to an Italian referral hospital and explore its association with clinical outcomes and the markers of disease severity. Methods In this single-center cohort study, 129 consecutive adult COVID-19 patients hospitalized in an Italian referral center were enrolled from March to April 2020. 25(OH)Vitamin D serum levels were assessed 48 hours since hospital admission and categorized into: normal (≥30 ng/mL), insufficient (

Emerging reports have described the possible occurrence of arthritis in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).1–3 Apart from crystal-induced arthritis,1 Yokogawa et al 2 and Alivernini et al 3 both described the onset of inflammatory arthritis with the characteristics of viral arthritis over the course of COVID-19. Here we would like to share a different case of monarthritis associated with psoriatic skin lesions presenting after resolution of SARS-CoV-2 infection. In April 2020, a patient in his 30s was admitted to our early arthritis outpatient clinic due to a 2-week history of painful limitation of the right elbow. The patient had no previous history of arthritis, back pain, enthesopathy, dactylitis, psoriasis (PsO) or other extra-articular symptoms of axial spondylarthritis, nor familiarity for rheumatic diseases and/or PsO. Forty days earlier, the patient had been suffering from arthromyalgia, fatigue, diarrhoea and anosmia, and had been diagnosed with COVID-19 based on reverse transcription (RT-PCR) detection of SARS-CoV-2 following nasopharingeal swab. Blood test analysis at …

The outburst of the novel COVID-19 has caused unprecedented stress in the healthcare systems and global economy since its outbreak in December 2019. Effective treatment for severely ill patients still needs to be identified, and many countries are still pushed by daily increases in case numbers and deaths. Furthermore, before a vaccine is made available or drugs eventually capable of preventing the infection are identified, exit strategies in those countries that have managed to bend the transmission curve are inevitably governed by trial and error. The alarm remains high also because COVID-19 flare-ups are increasingly likely and a second wave in fall is seen as a real risk. The effects of hydroxychloroquine (HCQ) on COVID-19 remain at the centre of intense debate. In the laboratory setting, HCQ has initially shown promise by interfering with the attachment, internalisation and replication of SARS-CoV-2,1 2 the causative agent of COVID-19. Additional benefits have been inferred from the capacity of HCQ to modulate inflammatory responses via toll-like receptor inhibition,3 possibly hindering the cytokine storm leading to acute respiratory distress syndrome,4 and to exert anticoagulatory activities5 capable of ameliorating COVID-19-related systemic thrombosis.6 Very recently, however, results from in vitro assays have not been confirmed in vivo in non-human primates.7 In parallel, the early enthusiasm on the clinical efficacy of HCQ on COVID-19 coming on top of small case series and open-label non-randomised trials8 9 has rapidly deflated following the dissemination of the results from large randomised clinical trials (RCTs). Three studies ceased enrolment early because of lack of efficacy of HCQ versus control arm in preliminary analyses.10–12 Similarly, according to rigorous RCTs recently published on high-impact medical journals, the use of HCQ did not result in higher probability of negative conversion13 or neither improved clinical status …

Interstitial lung disease (ILD) encompasses a wide range of parenchymal lung pathologies with different clinical, histological, radiological, and serological features. Follow-up, treatment, and prognosis are strongly influenced by the underlying pathogenesis. Considering that an ILD may complicate the course of any connective tissue disease (CTD) and that CTD's signs are not always easily identifiable, it could be useful to screen every ILD patient for a possible CTD. The recent definition of interstitial pneumonia with autoimmune features is a further confirmation of the close relationship between CTD and ILD. In this context, the multidisciplinary approach is assuming a growing and accepted role in the correct diagnosis and follow-up, to as early as possible define the best therapeutic strategy. However, despite clinical advantages, until now, the pathways of the multidisciplinary approach in ILD patients are largely heterogeneous across different centers and the best strategy to apply is still to be established and validated. Aims of this article are to describe the organization of our multidisciplinary group for ILD, which is mainly focused on the early identification and management of CTD in patients with ILD and to show our results in a 1 year period of observation. We found that 15% of patients referred for ILD had an underlying CTD, 33% had interstitial pneumonia with autoimmune feature, and 52% had ILD without detectable CTD. Furthermore, we demonstrated that the adoption of a standardized strategy consisting of a screening questionnaire, specific laboratory tests, and nailfold videocapillaroscopy in all incident ILD proved useful in making the right diagnosis.

Highlights • First reported case of Critical Illness-associated Cerebral Microbleeds in Covid-19. • EEG plays a crucial role in Covid-19 patients in the ICU. • Acute neurological complications should be explored systematically., Objectives We describe a patient suffering from Covid19-related acute respiratory distress syndrome (ARDS), highlighting the diagnostic role of the EEG in ICU. History A Covid-19 patient undergoing mechanical ventilation due to related acute respiratory distress syndrome (ARDS), presented altered mental status in the ICU. Video-EEG revealed a focal monomorphic theta slowing in bilateral frontal-central regions. Concordant with the EEG localization, MRI showed abundant microbleeds located in bilateral white matter junction, various regions of corpus callosum and internal capsule, suggestive of Critical Illness-Associated Cerebral Microbleeds. CSF analysis excluded the presence of encephalitis, SARS-Cov2 RNA-PCR in CSF was negative. Clinical and biological picture was suggestive of cytokine release syndrome. Conclusion This is the first reported case of Critical Illness-associated Cerebral Microbleeds in the context of Covid-19. Knowledge of Covid-19 is still partial and acute neurological complications should be explored systematically. In our case, EEG helped to rule out non-convulsive status epilepticus, but revealed focal dysfunction, justifying further investigations. EEG plays a crucial role in these patients, allowing investigating the presence of focal or diffuse cerebral dysfunction. This is particularly helpful for Covid-19 patients in the ICU, where the neurological examination is challenging by the severity of the respiratory illness.

Challenges in the provision of care and patients’ reluctance to access healthcare services and adhere to drug prescriptions in course of COVID-19 pandemic undermine the fundamental principles of early diagnosis and treat to target, which have revolutionised the natural history of many chronic inflammatory diseases starting from rheumatoid arthritis (RA).1 Although most rheumatologists have the impression that the intervals between symptom onset and first consultation have increased,2 no data currently indicate whether and to what extent the picture of early RA has changed during COVID-19. Here, we analysed data from the Pavia Early Arthritis Clinic (EAC) inception cohort. Referral criteria have been described previously, and include the presence of signs and symptoms of suspected inflammatory arthritis for

Differences in clinical presentation, response to treatment, and long-term outcomes between autoantibody-positive and -negative rheumatoid arthritis (RA) highlight the need for a better comprehension of the immunopathogenic events underlying the two disease subtypes. Whilst the drivers and perpetuators of autoimmunity in autoantibody-positive RA have started to be disclosed, autoantibody-negative RA remains puzzling, also due its wide phenotypic heterogeneity and its possible misdiagnosis. Genetic susceptibility appears to mostly rely on class I HLA genes and a number of yet unidentified non-HLA loci. On the background of such variable genetic predisposition, multiple exogeneous, endogenous, and stochastic factors, some of which are not shared with autoantibody-positive RA, contribute to the onset of the inflammatory cascade. In a proportion of the patients, the immunopathology of synovitis, at least in the initial stages, appears largely myeloid driven, with abundant production of proinflammatory cytokines and only minor involvement of cells of the adaptive immune system. Better understanding of the complexity of autoantibody-negative RA is still needed in order to open new avenues for targeted intervention and improve clinical outcomes.

The idiopathic inflammatory myopathies (IIMs) are a rare group of immune, systemic diseases characterised by muscle inflammation and frequently by extramuscular involvement. IIMs are heterogeneous with generally a chronic or subacute onset, which vary from less severe to more serious manifestations, not always easy to diagnose and even less to manage. In the past year, many studies have been published in order to clarify disease pathogenesis and improve patient management and treatment.The purpose of this review article is to provide an overview of the new insights in pathogenesis, serological findings, clinical manifestations and treatment of IIMs, summarising the most relevant studies published over the last year.

Background: Disease remission is recommended as the treatment target in patients with early rheumatoid arthritis (RA). According to the criterion, the proportion of patients classified as in remission considerably varies, with the Boolean-based definition being the most restrictive [1]. A considerable proportion of patients with established RA misses Boolean remission solely because of one of the 4 criteria (near remission) [2]. The frequency and the limiting variables to Boolean remission in real-life cohorts of patients with early RA are however unknown. Objectives: To assess the frequency and the limiting factors for fulfilling Boolean remission in early RA patients treated with csDMARDs according to a treat-to-target strategy. Methods: The study population consisted of 578 early RA patients ( Results: Complete follow-up data after 6 months of treatment were available for 89.3% of the patients. Disease remission was achieved in 25.6% of the cases according to the DAS28, 16.7% according to the simplified disease activity index (SDAI) and 11.6% according to the Boolean criterion. One-hundred and thirty-three patients (25.8%) failed to reach Boolean remission solely because of one of the 4 criteria. Of these, 45.9% were in DAS28 remission and 22.6% in SDAI remission. No differences in baseline demographic and clinical characteristics were found between patients in Boolean remission and patients in near remission. Use of prednisone co-medication and MTX starting dose were also comparable. Patients negative for both rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPA) were more frequently in near remission rather than in Boolean remission compared to autoantibody-positive patients (Fig. 1A). The missing criterion in near remission was SJC28 >1 in 49% of the cases, PGA >1 in 41%, and TJC28 >1 or CRP >1 mg/dl in the remaining 10%. Collectively, failure to achieve Boolean remission because of SJC28 >1 was more common in RF and/or ACPA positive patients. Rather, autoantibody-negative patients more frequently missed remission due to PGA (Fig. 1B). Conclusion: In patients with early RA treated with csDMARDs, near remission is up to two times more frequent than Boolean remission. Collectively, autoantibody-negative patients more commonly miss complete remission solely because of one criterion compared to autoantibody-positive patients. Furthermore, in these patients, failure to achieve remission is mostly related to high PGA rather than to the persistence of joint inflammation. Altogether, these findings implicate that autoantibody-negative RA patients failing to achieve remission would require adjunctive tailored interventions rather than reinforcement of DMARD therapy. References: [1] Mack ME, et al. Arthritis Rheumatol 2017;69:518-28. [2] Studenic P, et al. Ann Rheum Dis 2012;71:1702-5. Disclosure of Interests: Ludovico De Stefano: None declared, Serena Bugatti Speakers bureau: Bristol-Myers Squibb, Celgene, Lilly, Novartis, Sanofi, Janssen, Francesca Benaglio: None declared, Garifallia Sakellariou: None declared, Antonio Manzo: None declared, Roberto Caporali Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Roche, Genzyme, Lilly, MSD, Pfizer, UCB, Carlomaurizio Montecucco Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Sanofi, Genzyme, Lilly, MSD, Pfizer, UCB

Background: Dysphagia represents a frequent and disabling symptom in patients with Idiopathic Inflammatory Myopathies (IIMs) and it has been recently included in the new ACR/EULAR classification criteria for IIMs. Despite the clinical relevance, dysphagia assessment in IIMs is not currently standardized and evaluation tools are highly variable between different centers. Functional Endoscopic Evaluation of Swallowing (FESS) is an exam that allows, by using nasal endoscopy, the direct evaluation of anatomic structures and swallowing abilities in different swallowing phase. In fact, FESS could help the identification of different problems leading to dysphagia occurrence and to related dysphagia problems. Thanks to these characteristics, FESS for ENT specialists is the gold standard technique for evaluating swallowing functions. However, no studies so far have investigated the role of FESS in the assessment of IIMs and we are completely lacking a semeiotic description of FESS findings in these patients. Objectives: To provide the first semeiotic description of swallowing alterations evidenced by FEES in a cohort of IIMs patients. Methods: We retrospectively reviewed the FEES findings of IIMs patients performed at our hospital. Results: We enrolled 19 patients with a diagnosis of IIMs (10 patients were positive for a myositis specific antibody), of these 16 (84%) reported symptomatic dysphagia. We divided patients into 3 groups based on levels of peripheral muscle strength. Six patients (32%) had no clinical sign of active muscle disease (MRC scale 5, median CK 51 mU/ml, IQR 35-235), 5 patients (26%) had a mild reduction in muscle strength (MRC scale 4, median CK 76, IQR 54-220) and 8 patients (42%) showed a moderate-severe reduction in muscle strength (MRC scale ≤3, media CK 1440, IQR 628-6180). The 67% of patients without muscle disease activity showed an impairment in the oral phase of swallowing for solids and the 33% for fluids; 33% had a reduction in the activation of the pharyngeal phase of swallowing for both fluids and solids; only 17% of patients showed any sign of penetration, aspiration or pharyngeal residue for both solids and fluids. In the group of patients with moderate muscle activity, 80% of patients showed impairment in the oral phase of swallowing for solids and 40% for fluids; 60% had a reduction in the activation of the pharyngeal phase of swallowing for solids while 40% for fluids; 40% of patients showed signs of penetration, aspiration or pharyngeal residue for both solids and fluids. Finally, in the group of patients with severe muscle disease activity, 88% of patients showed an impairment in the oral phase of swallowing for solids and 50% for fluids; 63% had a reduction in the activation of the pharyngeal phase of swallowing for solids while 50% for fluids; 75% of patients showed signs of penetration, aspiration or pharyngeal residue for both solids and fluids. The 15% of all patients (3 cases, 1 from each group of muscle activity) showed a dysfunction in the upper esophageal sphincter. Of note, 3 patients (15%; 1 with moderate and 2 with severe muscle disease activity) required nutrition through nasogastric tube. Conclusion: We showed that FESS study identified swallowing dysfunctions in both the oral and pharyngeal phases of swallowing. Swallowing dysfunctions were more prevalent in patients with greater muscle involvement; however, alterations were not rare also in patients with no clinical signs of muscle activity and, in particular, in the few patients without reported symptoms of dysphagia. FEES appears as a useful tool for the evaluation of dysphagia in IIMs. Reference [1] Brady S, Otolaryngol Clin North Am. 2013Dec;46(6):1009-22 Disclosure of Interests: Emiliano Marasco: None declared, Giulia Bertino: None declared, Ludovico De Stefano: None declared, Lorenzo Volpiano: None declared, Pietro Canzi: None declared, Marco Benazzo: None declared, Carlomaurizio Montecucco Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Sanofi, Genzyme, Lilly, MSD, Pfizer, UCB, Lorenzo Cavagna: None declared

Background: Myositis specific antibodies play a central role in the assessment of idiopathic inflammatory myopathies (IIMs) as their presence may indicate specific disease subsets/manifestations or cancer risk. At present, anti-MDA5 antibodies have been associated with the occurrence of rapidly progressive interstitial lung disease (RP-ILD), a life-threatening condition, generally refractory to treatment. Objectives: To describe the relationship between malignancy and anti-MDA5 antibodies in IIMs. Methods: Patients with anti-MDA5+ IIMs and a history of cancer were included in this study. Data were retrospectively collected. Because of the lack of RP-ILD shared definitions, we defined RP-ILD as an admission to the Intensive Care Unit (ICU) for IIMs related respiratory insufficiency. Results: In our cohort (n=133, 67% females) we identified 17 patients (13%) with a history of cancer (8 males [47%], 9 females [53%]; median age at IIMs onset 62 years [IQR 53-67], at cancer diagnosis 56 years [IQR 51-66]). All but 1 patient had solid tumours, 5 (29%) had breast cancer. In 9 patients (53%) cancer diagnosis ranged ± 3 years from IIMs onset; in 3 patients the delay exceeded 120 months. Three patients (18%) developed RP-ILD respectively 82, 66 and 0 months after the diagnosis of cancer. Four (24%) patients died respectively 0 (neoplasia), 0 (RP-ILD in ICU, diagnosis of cancer after an autopsy), 7 (neoplasia) and 66 (infection after RP-ILD in ICU) months after cancer diagnosis. The 13 surviving patients had a median rheumatological follow-up of 47 months (IQR 19-84) and an oncological follow-up of 57 months (IQR 10-130). Interestingly, in the overall cohort 66% of patients without cancer (76 out of 116) had less than 3 years of follow-up. Of the 22 RP-ILD patients without neoplasia 14 died, 11 during ICU admission. In the latter patients, we could not rule out an occult neoplasia due to the emergency of the situation. Only one patient, with a 18 month history of IIMs before ICU admission, underwent autopsy and was reported negative for cancer. Conclusion: This is the first study addressed to tackle the relationship between cancer and anti-MDA5+ IIMs. Although in some cases no clear relationship between IIMs and cancer can be proved because of the time gap, in others the timing of occurrence of cancer and IIMs was very close, suggesting a link between these manifestations. Finally, we emphasize the importance of an accurate neoplasm screening in anti-MDA5+ RP-ILD, because treatment refractoriness could suggest the paraneoplastic nature of the manifestation. References [1] Barsotti S, et al. Rheumatol Int 2014 [2] Lu X, et al. PLoS One 2014 Disclosure of Interests: Ludovico De Stefano: None declared, Santos Castaneda Consultant for: Amgen, BMS, Pfizer, Lilly, MSD, Roche, Sanofi, UCB, Ellen De Langhe: None declared, Jorg Distler: None declared, Johannes Knitza: None declared, Ilaria Cavazzana: None declared, alain meyer: None declared, Jorge Rojas-Serrano: None declared, eugenio arrigoni: None declared, Federica Furini: None declared, Marcello Govoni Paid instructor for: Pfizer, Roche, Speakers bureau: Pfizer, Abbvie, MSD, Roche, Eli-Lilly, Celgene, Sanofi, Janssen, paola parrocchini: None declared, Giovanni Zanframundo: None declared, Jose Antonio P. da Silva: None declared, elisa pedrollo: None declared, Florenzo Iannone Consultant for: F Iannone has received consultancy fees and/or speaker honoraria from Pfizer, AbbVie, MSD, BMS, Novartis, Lilly, UCB outside this work, Speakers bureau: F Iannone has received consultancy fees and/or speaker honoraria from Pfizer, AbbVie, MSD, BMS, Novartis, Lilly, UCB outside this work, Carlomaurizio Montecucco Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Sanofi, Genzyme, Lilly, MSD, Pfizer, UCB, Lorenzo Cavagna: None declared

In light of their increased risk of worst outcomes following COVID-19 infection, patients with rheumatic and musculoskeletal diseases (RMDs) on immunosuppressive therapy, including systemic glucocorticoids, biological (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs), represent a vulnerable population which should be prioritised to receive vaccination. Controlled data on the effectiveness and safety of different COVID-19 vaccines on patients with RMD are not available yet. However, rheumatology providers and health professionals should be ready to offer timely guidance for the optimal use of vaccines for patients on immunomodulatory drugs. Based on the long-time experience with other non-live vaccines, the COVID-19 Task Force of the European League Against Rheumatisms (EULAR) first delivered a preliminary set of information in December 2020.1 Overall, it is expected that the safety and immunogenicity of COVID-19 vaccines for most of the DMARDs will be comparable with that registered for the general population,2–4 so that postponing vaccination pending more information appears unjustified. A number of independent surveys have however alarmingly reported that, among patients with RMD, potential acceptance of COVID-19 vaccines may not exceed 60%, without apparent differences in relation to specific diseases, comorbidities and type of medication.5–8 Strategies to effectively engage high-risk patients with RMD into vaccination programmes are therefore urgently needed. Starting from 19 March 2021, rheumatologists of the IRCCS Policlinico San Matteo University Hospital of Pavia, Italy, have been actively involved in the vaccination campaign by personally contacting, booking and administering COVID-19 vaccines to patients with RMD on b/tsDMARDs followed at …

We present the case of a woman who, in association with a rupture of a breast implant, a few years later, developed fibromyalgia together with a myofibrillar myopathy with abundant cytoplasmic rods. Such myopathy, despite microscopic inflammatory changes and the increased ANA and anti-ENA (anti-CenpB), showed a poor inflammatory character and was highly suggestive of sporadic late onset nemaline myopathy (SLONM). SLONM is a sporadic myopathy described in association with MGUS or, less frequently, multiple myeloma, or in association with autoimmune disorders, such as Sjogren's syndrome, systemic lupus erythematosus and dermatomyositis. To our best knowledge, this type of myofibrillar myopathy has been not previously described neither in association to Silicone implant incompatibility syndrome (SIIS) nor to immunoinflammatory mechanisms potently triggered by silicone.

A significant proportion of patients with rheumatoid arthritis (RA) misses the target of disease remission solely because of the patient global assessment of disease activity (PGA) exceeding the cut-off of 1.1–5 As PGA may also reflect non-inflammatory symptoms, its inclusion as a driver of intensification of immunosuppressive therapy is currently been questioned.6 Complete omission of the patients’ perspective, however, impairs functional outcomes and the ability to discriminate effective treatments from placebo.7 As such, different thresholds for the PGA are being tested, with a recent proposal from randomised clinical trials suggesting a suitable cut-off of 2.8 Here, we evaluated the performance of modifying the Boolean definition of remission9 by increasing the cut-off of the PGA to 28 in real life. Data were retrieved from 826 consecutive patients from two University Hospitals with an observation period of 12 months. Five hundred and thirty-five were patients with early RA (median (IQR) symptoms’ duration 16 [9–28] weeks) started on …

OBJECTIVES We realized a longitudinal open-label study to determine if increasing intervals between etanercept (ETN) administration could be effective in maintaining remission with a stable dose in a patient population affected by psoriatic arthritis (PsA) who had achieved sustained remission with ETN 25 mg biweekly. METHODS Fifty-four PsA patients were recruited at the Rheumatology Unit of Azienda Ospedaliera Universitaria Senese. Patients, who were in clinical sustained remission with biweekly ETN 25 mg at weeks 12 and 16, and were switched to a weekly regimen. If clinical remission persists at weeks 24 and 28, patients were switched to an every-other-week regimen, continuing with this administration schedule for the entire duration of the study if at weeks 36 and 40 clinical remission was maintained. If, on the contrary, in one of the check there was an increase in disease activity, the therapeutic scheme returned to the previous one. RESULTS The results of our study indicate that a consistent percentage (72%) of subjects with PsA, achieving a sustained remission with ETN 25 mg biweekly, maintains a remission, after a year of starting therapy, despite a progressive dose reduction by an increase in the dosing interval, 21% with a weekly regimen and 51% with an every-other-week regimen. CONCLUSIONS Our results show that the main reasons that hinder the dosing interval increase in ETN in PsA patients in sustained clinical remission at standard doses are peripheral polyarthritis pattern and exacerbation of cutaneous manifestations.