Search

COVID-19; Registries; Vaccination COVID-19; Registros; Vacunación COVID-19; Registres; Vacunació Vaccine hesitancy is considered a major barrier to achieving herd immunity against COVID-19. While multiple alternative and synergistic approaches including heterologous vaccination, booster doses, and antiviral drugs have been developed, equitable vaccine uptake remains the foremost strategy to manage pandemic. Although none of the currently approved vaccines are live-attenuated, several reports of disease flares, waning protection, and acute-onset syndromes have emerged as short-term adverse events after vaccination. Hence, scientific literature falls short when discussing potential long-term effects in vulnerable cohorts. The COVAD-2 survey follows on from the baseline COVAD-1 survey with the aim to collect patient-reported data on the long-term safety and tolerability of COVID-19 vaccines in immune modulation. The e-survey has been extensively pilot-tested and validated with translations into multiple languages. Anticipated results will help improve vaccination efforts and reduce the imminent risks of COVID-19 infection, especially in understudied vulnerable groups. HC is supported by the National Institution for Health Research Manchester Biomedical Research Centre Funding Scheme. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.

We aim to perform ultrastructural and histopathological analysis of muscle biopsies from a large group of systemic sclerosis (SSc) patients, including some with early/mild SSc features, and examine whether capillary pathology differentiates 'scleromyositis' (SM) from other auto-immune myositis (AIM) subsets.Muscle biopsies from a total of 60 SM patients and 43 AIM controls from two independent cohorts were examined by electron microscopy, collagen-4 immunofluorescence (Col4IF) and routine light microscopy.Ultrastructural examination revealed prominent capillary basement membrane (BM) reduplication (4+ layers in50% of capillaries) in 65% of SM vs 0% of AIM controls (p 0.001). In SM cases without prominent BM reduplication, capillary dilation was the most distinctive feature, present in 8% of capillaries in SM vs 2% in controls (p = 0.001). Accumulation of ensheathed pericyte processes was another characteristic feature of SM and closely correlated with the degree of BM reduplication (r = 0.833, p 0.001). On light microscopy, BM marker Col4IF revealed more frequent capillary enlargement in SM than in controls (84% vs 21%, p 0.001). SM cases were classified as non-inflammatory myopathy (36%), non-specific myositis (33%) or immune-mediated necrotizing myopathy (31%), but despite this histopathological heterogeneity, prominent BM reduplication remained a constant finding. In the 16 SM patients with early/mild SSc features, 63% showed prominent BM reduplication.These results show that capillary pathology, and in particular prominent capillary BM reduplication, is the hallmark histopathological feature of SM even in patients with early/mild SSc and support the concept of SM as an organ manifestation of SSc and a distinct subset of AIM.

Objective Dysphagia is a life-threating manifestation of idiopathic inflammatory myopathies (IIM). However, we lack a univocal protocol for its treatment. The aim of this retrospective analysis was to evaluate the effectiveness of a step-up strategy by adding a 1-day pulse of IVIGs to immunosuppressants in IIM patients with refractory dysphagia diagnosed by Eating Assessment Tool (EAT)-10 and fibreoptic endoscopic evaluation of swallowing (FEES). Methods Dysphagia was defined as a pharyngo-oesophageal disturbance associated with EAT-10 score ≥3 and at least one FEES abnormality among propulsion failure, solid or liquid stasis. Eighteen out of 154 IIM patients had FEES-confirmed dysphagia and underwent 1 day IVIG 2 g/kg repeated 1 month apart for 3 months, because of dysphagia refractory to high-dose glucocorticoids with methotrexate and/or azathioprine. Clinical characteristics along with myositis-specific antibodies and muscle histopathological findings were studied in FEES-dysphagia IIM and IIM control patients. Results After three monthly doses of IVIG, EAT-10 score dropped with complete recover of defective propulsion and progressive decrease in percentage of both solid and liquid stasis. At 52-weeks’ follow-up, reached in 12 patients, all these parameters were stable or further improved. An improvement in manual muscle strength test and a steroid-sparing effect of IVIG were also observed. Anti-PM/Scl 75/100 antibodies were much more frequent in the FEES-dysphagia group, while anti-Jo1 antibody was rarely detected. Conclusion Our treatment schedule with 2 g/kg IVIG was effective for IIM-associated refractory dysphagia assessed by the combination of EAT-10 and FEES. These findings need to be prospectively tested in a larger cohort of IIM patients.

Background: The post-COVID-19 condition, defined as COVID-19-related signs and symptoms lasting at least 2 months and persisting more than 3 months after infection, appears now as a public health issue in terms of frequency and quality of life alterations. Nevertheless, few data are available concerning long term evolution of malnutrition and sarcopenia, which deserve further attention. Method: Sarcopenia was investigated prospectively, together with weight evolution, at admission and at 3 and 6 months after hospital discharge in 139 COVID-19 patients, using the European Working Group on Sarcopenia in Older People (EWGSOP2) criteria, associating both decreased muscle strength and muscle mass, assessed, respectively, with hand dynamometer and dual-energy X-ray absorptiometry. Results: Of the 139 patients, 22 presented with sarcopenia at 3 months; intensive care units (ICU) length of stay was the sole factor associated with sarcopenia after multivariate analysis. Although the entire group did not demonstrate significant weight change, weight decreased significantly in the sarcopenia group (Five and eight patients, showing, respectively, >5 or >10% weight decrease). Interestingly, at 6 months, 16 of the 22 patients recovered from sarcopenia and their weight returned toward baseline values. Conclusions: Sarcopenia and malnutrition are frequently observed in patients hospitalized for COVID-19, even 3 months after infection occurrence, but can largely be reversed at 6 months after discharge. Enhanced patient care is needed in sarcopenic patients, particularly during long stays in an ICU.

© 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.

Background The risk of severe COVID-19 and its determinants remain largely unknown in patients with autoimmune and inflammatory rheumatic diseases. The objective of this study was to assess the prevalence of COVID-19 infection in patients followed for rare autoimmune diseases as well as the predictors of COVID-19 and disease flare-ups. Methods Cross-sectional phone survey from April 9, 2020, to July 2, 2020, during which patients with autoimmune diseases followed at the National Reference Center for Rare Autoimmune diseases of Strasbourg were systematically contacted by phone and sent a prescription for a SARS-CoV-2 serology. Results One thousand two hundred thirty-two patients were contacted. One thousand fifty-five patients with a confirmed diagnosis of systemic autoimmune disease were included (4 unreachable, 4 moves abroad, 5 deaths before pandemic, 50 without consent, and 114 without autoimmune disease). Among them, 469 (44.5%) patients were tested for SARS-CoV-2 serology. Thirty-nine patients (7.9%) had SARS-CoV-2 infection (either through chest CT-scan [n = 5], RT-PCR on nasopharyngeal swab [n = 14], or serology [n = 31]) among the 496 who underwent at least one of those 3 diagnosis modalities. Of the 39 proven cases, 33 had clinical manifestations (6 asymptomatic patients were diagnosed through systematic serology testing), 31 were managed by home care, 3 were hospitalized due to a need for oxygenation, two required admission to an intensive care unit, and one died. Among patients with confirmed SARS-CoV-2 infection, reported flares were more frequent than in uninfected patients (26.3% [10/38] vs. 7.0% [32/457], p Overall, the seroprevalence of SARS-CoV-2 was 6.6% (31/469) which was numerically lower to the Grand-Est general population estimated to be 9.0%. Conclusions This systematic survey of more than 1000 patients with rare systemic autoimmune diseases reports a low prevalence of proven SARS-CoV-2 infection and very rare severe infections, probably related to good compliance with prophylactic measures in these patients.

Introduction The molecular mechanism of immune-mediated necrotizing myopathy (IMNM) remains unknown. Autophagy impairment, described in autoimmune diseases, is a key process in myofiber protein degradation flux and muscle integrity and has not been studied in IMNM. Methods Muscle biopsies from patients with IMNM (n = 40), dermatomyositis (DM; 24), polymyositis (PM; 8), polymyositis with mitochondrial pathology (4), sporadic inclusion body myositis (8), and controls (6) were compared by immunohistochemistry. Results The proportions of myofibers containing autophagy markers LC3b and p62 were higher in IMNM than in DM or PM and correlated with creatine kinase levels. In IMNM, compartmentalized LC3b puncta were located in regenerating and degenerating myofibers surrounded by major histocompatibility complex type II+ inflammatory cells. Several IMNM myofibers accumulated ubiquitin and misfolded protein. Discussion The detection of LC3b+ or p62+ myofibers could be used in differentiating IMNM from PM. The identification of autophagy-modifying molecules potentially could improve patients' outcomes. Muscle Nerve, 2019.

Objective The aim of our study was to investigate clinical and histopathological findings in adult DM patients positive for anti-Mi2 (anti-Mi2+) antibodies compared with DM patients negative for anti-Mi2 (anti-Mi2–). Methods Clinical data of adult DM patients, who fulfilled EULAR/ACR 2017 classification criteria, were gathered from electronic medical records of three tertiary Rheumatology Units. Histopathological study was carried out on 12 anti-Mi2+ and 14 anti-Mi2– muscle biopsies performed for diagnostic purpose. Nine biopsies from immune mediated necrotizing myopathy (IMNM) patients were used as control group. Results Twenty-two anti-Mi2+ DM [90.9% female, mean age 56.5 (15.7) years] were compared with 69 anti-Mi2– DM patients [71% female, mean age 52.4 (17) years]. Anti-Mi2+ patients presented higher levels of serum muscle enzymes than anti-Mi2– patients [median (IQR) creatine-kinase fold increment: 16 (7–37)vs 3.5 (1–9.9), P 0.05]. In addition, the endomysial macrophage score was similar between anti-Mi2+ and IMNM patients [mean 1.2 (0.9) vs 1.3 (0.5), P >0.05], whereas lower macrophage infiltration was found in anti-Mi2– DM [mean 0.4 (0.5), Conclusions Anti-Mi2+ patients represent a specific DM subset with high muscle damage. Histological hallmarks were a higher prevalence of myofiber necrosis, endomysial involvement and macrophage infiltrates at muscle biopsy.

The coronavirus disease-2019 (COVID-19) pandemic continues to be a cause of unprecedented global morbidity and mortality. Whilst COVID-19 vaccination has emerged as the only tangible solution to reducing poor clinical outcomes, vaccine hesitancy continues to be an obstacle to achieving high levels of vaccine uptake. This represents particular risk to patients with autoimmune diseases, a group already at increased risk of hospitalization and poor clinical outcomes related to COVID-19 infection. Whilst there is a paucity of long-term safety and efficacy data of COVID-19 vaccination in patients with autoimmune diseases, the current evidence strongly suggests that the benefits of vaccination outweigh the risks of adverse effects and disease flares. Herein, we report the protocol of the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study, an ongoing international collaborative study involving 29 countries and over 110 investigators. Supplementary Information The online version contains supplementary material available at 10.1007/s00296-021-05046-4.

Objective We recently recorded a high prevalence of inclusion body myositis (IBM) in patients with Sjögren’s syndrome (SS). Whether myositis patients with SS differ from myositis patients without SS in terms of the characteristics of the myositis is currently unknown. Anti-cytosolic 5′-nucleotidase 1 A (cN1A) has recently been proposed as a biomarker for IBM but is also frequent in SS. Whether anti-cN1A is independently associated with IBM is still an open question. We aimed to assess the significance of SS and anti-cN1A in myositis patients. Methods Cumulative data on all myositis patients (EULAR/ACR 2017 criteria) screened for SS (ACR/EULAR 2016 criteria) in a single centre were analysed. Ninety-nine patients were included, covering the whole spectrum of EULAR/ACR 2017 myositis subgroups and with a median follow-up of 6 years (range 1.0–37.5). The 34 myositis patients with SS (myositis/SS+) were compared with the 65 myositis patients without SS (myositis/SS-). Results . IBM was present in 24% of the myositis/SS+ patients vs 6% of the myositis/SS- group (P = 0.020). None of the IBM patients responded to treatment, whether they had SS or not. Anti-cN1A was more frequent in myositis/SS+ patients (38% vs 6%, P = 0.0005), independently of the higher prevalence of IBM in this group (multivariate P value: 0.02). Anti-cN1A antibody specificity for IBM was 0.96 (95% CI: 0.87, 0.99) in the myositis/SS- group but dropped to 0.70 (95% CI: 0.48, 0.85) in the myositis/SS+ group. Interpretation In myositis patients, SS is associated with IBM and with anti-cN1A antibodies, independently of the IBM diagnosis. As a consequence, anti-cN1A has limited specificity for IBM in myositis patients with SS.

Objectives To refine the prevalence, characteristics and response to treatment of myositis in primary SS (pSS). Methods The multicentre prospective Assessment of Systemic Signs and Evolution in Sjögren’s Syndrome (ASSESS) cohort of 395 pSS patients with ≥60 months’ follow-up was screened by the 2017 EULAR/ACR criteria for myositis. Extra-muscular complications, disease activity and patient-reported scores were analysed. Results Before enrolment and during the 5-year follow-up, myositis was suspected in 38 pSS patients and confirmed in 4 [1.0% (95% CI: 0.40, 2.6)]. Patients with suspected but not confirmed myositis had higher patient-reported scores and more frequent articular and peripheral nervous involvement than others. By contrast, disease duration in patients with confirmed myositis was 3-fold longer than without myositis. Two of the four myositis patients fulfilled criteria for sporadic IBM. Despite receiving three or more lines of treatment, they showed no muscle improvement, which further supported the sporadic IBM diagnosis. The two other patients did not feature characteristics of a myositis subtype, which suggested ‘pure’ pSS myositis. Steroids plus MTX was then efficient in achieving remission. Conclusions Myositis, frequently suspected, occurs in 1% of pSS patients. Especially when there is resistance to treatment, sporadic IBM should be considered and might be regarded as a late complication of this disease.

Since the end of 2019, the coronavirus disease 2019 (COVID-19) pandemic has struck worldwide, leading to more than 7 million cases by June 2020, with an approximately 5.5% mortality rate, mainly due to acute respiratory distress syndrome (ARDS) [1]. We thank Mrs Pragnell Babette for her English support.

Background Scleromyositis (SM) is an emerging subset of myositis associated with features of systemic sclerosis (SSc) but it is currently not recognized as a distinct histopathological subset by the European NeuroMuscular Center (ENMC). Our aim was to review studies reporting muscle biopsies from SSc patients with myositis and to identify unique histopathological features of SM. Methods A scoping review was conducted and included all studies reporting histopathological findings in SSc patients with myositis searching the following databases: PubMed, MEDLINE, EMBASE, CINAHL and EBM-Reviews. Clinical, serological, and histopathological data were extracted using a standardized protocol. Results Out of 371 citations, 77 studies that included 559 muscle biopsies were extracted. Fifty-seven percent (n = 227/400) had inflammatory infiltrates, predominantly T cells, which were endomysial (49%), perimysial (42%) and perivascular (41%). Few studies (18%, n = 8/44) evaluated the presence of B-cells. Myofiber atrophy was present in 48% (n = 104/218) of biopsies, and was predominantly perifascicular in 19% (n = 6/31), with necrosis reported in 56% (n = 162/290) of cases. Sarcolemmal MHC-I upregulation was found in 72% (n = 64/89) of biopsies. Non-specified C5b-9 deposition was described in 39% of muscle biopsies (n = 28/72). Neurogenic features were present in 23% (n = 44/191); endomysial fibrosis was reported in 35% (n = 120/340); and rimmed vacuoles were observed in 32% (n = 11/34) of biopsies. Capillaropathy, such as capillary dropout and/or ultrastructural endothelial abnormalities, was reported in 33% (n = 43/129) of cases. Reported ENMC categories were mainly polymyositis (21%), non-specific myositis (19%), immune-mediated necrotizing myopathy (16%), and dermatomyositis (8%). Histopathological features were analyzed according to serological subtypes in 28 studies, including anti-PM-Scl (n = 48), -Ku (n = 23) and -U1RNP (n = 90). Most of these biopsies demonstrated inflammatory infiltrates (range 49–85%) as well as MHC-I expression (range 63–81%). Necrosis was associated with anti-Ku (85%) and anti-U1RNP (73%), while anti-Ku was also associated with neurogenic features and rimmed vacuoles in 57% and 25% of cases, respectively. Conclusion Our review suggests that SM is characterized by heterogeneous pathological features using definitions included in current histopathological criteria. Whether a distinct histopathological signature exists in SM remains to be determined. SSc-specific and SSc-associated autoantibodies may help define more homogeneous histopathological subsets.

Objective Arthritis, myositis and interstitial lung disease (ILD) constitute the classic clinical triad of anti-synthetase syndrome (ASSD). These patients experience other accompanying features, such as Raynaud's phenomenon, fever or mechanic's hands. Most ASSD patients develop the complete triad during the follow-up. In the present study we aimed to determine whether the subsequent appearance of accompanying features may suggest the development of triad findings lacking at the onset in anti-Jo1 positive ASSD patients. Methods Anti-Jo1 positive patients presenting with incomplete ASSD (no >2 classic triad features) were assessed. Clinical characteristics and clusters of disease manifestations were retrospectively collected and analyzed in a large international multicenter cohort of ASSD patients. Results 165 patients (123 women) with incomplete ASSD were identified. Ninety-five patients (57.5%) developed new classic triad manifestations after 15months median (IQR 9–51) and 40 (24%) developed new accompanying features after 19months median (IQR 6–56) from disease onset. During the follow-up, the ex-novo occurrence of triad features was observed in 32 out of 40 patients (80%) with new accompanying findings and in 63 out of 125 patients (50.5%) without new accompanying findings (p=0.002). In patients with at least one new accompanying feature the odds ratio for the occurrence of new triad manifestations was 3.94 with respect to patients not developing ex-novo accompanying findings (95% CI 1.68–9.21, p=0.002). Conclusion Anti-Jo1 ASSD patients with incomplete forms at disease onset are at high risk for the subsequent occurrence of lacking classic triad findings. Although all ASSD patients should be carefully assessed for the occurrence of new triad features, a closer follow-up should be considered in the subgroup of patients developing ex novo accompanying findings. These patients, indeed, have near four-fold increased risk for new classic triad manifestation occurrence with respect to patients not presenting ex novo accompanying findings.

Background IL-6r targeting therapy has been proven to be effective and safe in Giant Cell arteritis (GCA) as well in Takayasu arteritis (TA) in RCTs, probably because of the similar pathologic findings and vessel size (Large Vessel Vasculitis, LVV). However, real world data are scarce. Objectives The aim of the study was to evaluate the effectiveness of Tocilizumab for LVV in real life settings. Methods We retrospectively evaluated, from 2011 to 2017, the outcomes (including glucocorticoid dosage) in patients affected by LVV (according to 1990 aCR classification criteria) who received 8 mg/kg iv Tocilizumab (TCZ) monthly, due to the inadequate response to immunosuppressant. Demographic and clinical characteristics and laboratory findings were collected at baseline and consecutive follow up visits, over 52 weeks. Statistical analysis was performed using the GraphPad Software ver. 6.0 (San Diego CA USA) using appropriate tests. Results We analyzed n.10 patients (6/10 GCA, 4/10 TA) with mean age (± SD) 56 ± 21 years and mean disease duration 41±38 months. Eight out of 10 patients were female. Over the entire observation period, 7/10 also received concomitant methotrexate (mean dose 12.8 ± 2.7 mg/week) while 2/10 received azathioprine (100 mg/day). Median (IQR) prednisone equivalent dose at baseline was 22.5 (10-25) mg/day. At baseline, median ESR was 49 (31-58) mm/h and median CRP level was 15.4 (1.95-28.53) mg/l. Upon TCZ treatment we observed a good disease control in absence of headache, fever and other LVV clinical signs through 52-week follow up. At 52 weeks, we observed a significant reduction of ESR down to 6.5 (2.75-12.25) mm/h as well as of CRP level, down to 1.5 (0.67-3.47) mg/l (p Conclusion In our real life experience iv TCZ was effective and safe in LVV treatment, with a good disease control and a significant steroid-sparing effect. Our preliminary findings need to be confirmed in larger cohorts and prolonged follow-up. References [1] Stone JH, Tuckwell K, Dimonaco S, Klearman M, aringer M, Blockmans D, Brouwer E, Cid MC, Dasgupta B, Rech J, Salvarani C, Schett G, Schulze-Koops H, Spiera R, Unizony SH, Collinson N. Trial of Tocilizumab in Giant-Cell arteritis. N Engl J Med. 2017Jul27;377(4):317-328. doi: 10.1056/NEJMoa1613849. PubMed PMID: 28745999. Disclosure of interests giulia righetti: None declared, vincenzo venerito: None declared, maria giannotta: None declared, Giuseppe Lopalco Speakers bureau: SOBI, BMS, margherita giannini: None declared, Fabio Cacciapaglia: None declared, Laura Coladonato: 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

Background:COVID-19 survivors may have high risks of developing sarcopenia, which is associated to handicap, poor quality of life, higher healthcare costs, increased risk of falls, increased mortality (1).Objectives:To assess sarcopenia rate (which has not been described yet) following COVID-19 hospitalization and to highlights features associated with sarcopenic vs. non-sarcopenic patients.Methods:Major confirmed COVID-19 patients undergoing intensive care unit (ICU) or Pneumology Department admission in Strasbourg University Hospital between March and June 2020 were prospectively included. Muscle and cardio-respiratory evaluations were performed 3 months after discharge. Sarcopenic patients were compared to non-sarcopenic ones. A second muscle assessment 6 months after discharge was performed in patients with pathologic muscle tests.Results:127 patients were included, 39 (30.7%) not requiring ICU care, 88 (69.3%) requiring ICU care. The cohort consisted of 71% male patients, with a median age of 63 years [28-82]. Forty-one-percent were obese (BMI>30 kg/m2). Most individuals had preexisting comorbidities (82 patients, 70%), mainly hypertension and diabetes mellitus. The median total hospital stay duration was 22 days and up to 89 days. At the 3 months assessment, 17/127 (13%) patients were diagnosed with sarcopenia which comprised 6/17 (35%) severe sarcopenia (4.7% of the total cohort). At the 6 months assessment, only 4/15 (27%) of the initial sarcopenic patients remained sarcopenic (3% of the total cohort) and 3 of these 4 patients had severe sarcopenia. BMI (26,3 vs. 29,3, p=0.03), COPD (20% vs. 3%, p=0.03), comorbidities (93% vs. 67%, p=0.04), total hospital stay duration (33 vs. 20 days, p=0.03) and ICU stay duration (33 vs. 13 days, p=0.01) were significantly associated with sarcopenic vs. no sarcopenic patients. However, there was no significant difference concerning cardio-pulmonary evaluations between these two groups.Conclusion:We here highlighted a sarcopenia prevalence at 3 and 6 months following a hospitalization for COVID-19 of 13% and 3% respectively, occurring mainly in patients with comorbidities. Sarcopenia was not associated to worse cardio-pulmonary results in comparison with non-sarcopenic patients.References:[1]Di Filippo L, De Lorenzo R, D’Amico M, Sofia V, Roveri L, Mele R, et al. COVID-19 is associated with clinically significant weight loss and risk of malnutrition, independent of hospitalisation: A post-hoc analysis of a prospective cohort study. Clinical Nutrition [Internet]. oct 2020. https://linkinghub.elsevier.com/retrieve/pii/S0261561420305896Disclosure of Interests:None declared

Background:Myositis are systemic autoimmune rare diseases characterized by muscle inflammation and weakness. Even though the signs of active disease have been resolved, myositis patients frequently present residual muscle weakness, decreased physical performance and sustained disability. This condition has been coined on the term “damage” (as opposed to “activity”).Sarcopenia is a frequent, progressive and generalized skeletal muscle disorder characterized by low muscle strength and mass leading to handicap, decreased quality of life and increased mortality.1Prevalence and significance of sarcopenia in myositis patients has never been reported.Objectives:To study sarcopenia in myositis patients with low or no disease activity.Methods:Adult myositis patients (2017 ACR/EULAR criteria), with disease duration greater than 12 months, creatine kinase serum level (CK) less than 500 U/l, stable medication for 6 months were enrolled. Patients with inclusion body myositis were excluded. Total (LM) and appendicular (ALM) muscle mass were measured using dual-energy X-ray absorptiometry (DXA, Hologic) and muscle grip strength was measured using Jamar dynamometer. Sarcopenia was defined according to the EWGSOP2 consensus.1Results:29 patients (20 female, 68.9%), with a median age of 61 years (50.5-71) were enrolled. They suffered from dermatomyositis (DM, n=4), immune-mediated necrotizing myopathy (IMNM), n=8), anti-synthetase syndrome (ASS, n=9), scleromyositis (SM, n=8) since 4.7 years (2.8-8.3). At the evaluation, muscle strength assessed with MMT-8 was 139/150 (136-147), MMT-12 was 210/220 (204-216) and CK were 131.5 U/l (105.5-202). Four patients (13.8%) were sarcopenic. Sarcopenic patients were older (73.4 years (66.2-80.5) vs 58.7 years (44.2-79.6), p=0.03), with a longer disease duration (7.3 years (5.3-11.8) vs 4.3 (2.7-8.3), p = 0.1), longer time with increased CK (449 days (169.8-954) vs 255.5 (124-872.8)), higher maximum CK values (6000 U/l (2205-7000) vs 1636 (900-4457)). They suffered from IMNM (2/4, 50%); DM (n=1) and SM (n=1), had more frequently disease-related cardiac involvement (50% vs 4%, p=0.04), and tended to a longer steroid therapy duration (2.4 years (0.8-5) vs 1.8 (1.3-3.9), p=0.9) and a higher number of immunomodulatory drugs (2.5 (2-5.3) vs 2 (2-3), p=0.3).At the evaluation, sarcopenic patients were globally weaker as highlighted by lower MMT-12 (201 (196.8-206.8) vs 213 (207-217.5), p=0.02). Head flexo-extensors and proximal upper muscles were especially weaker (respectively, p=0.04 and p=0.03). Muscle performance was also lower in sarcopenic patients as assessed by distance covered at 6-minute walk test (6mWT, p=0.003) and number of squats in 30 seconds (p=0.005). Time to drink a glass of water was significantly longer in sarcopenics (p=0.04) even if any patient referred dysphagia. Health assessment questionnaire score was greater (1.4 (0.8-2) vs 0.6 (0.2-1), p=0.04) indicating higher handicap. LM positively correlated with MMT-8 (ρ=0.5, p=0.01) and MMT-12 (ρ=0.5, p=0.004), with number of squats in 30 seconds (ρ=0.7, p=0.0003) and 6mWT distance covered/lower limit (ρ= 0.5, p=0.01). Moreover, LM negatively correlated with time to drink a glass of water (ρ=-0.6, p=0.002).Conclusion:Muscle mass measured by DXA is a relevant parameter for muscle damage and disability in myositis patients. Sarcopenic myositis patients represent a subgroup with important muscle damage and handicap.References:[1]Cruz-Jentoft AJ et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 1 Jan 2019;48(1):16-31.Disclosure of Interests:None declared

Background:Myositis are rare autoimmune diseases, affecting more women than men, characterized by chronic inflammation of skeletal muscle causing muscle weakness, decreased quality of life and increased mortality.Glucocorticoids (GC) are potent anti-inflammatory drugs, and are the first line treatment of myositis. They improve muscle strength of myositis patients (therapeutic effect), yet muscle recovery is generally only partial. Moreover, GC have an iatrogenic effect on skeletal muscle fibre leading to steroid myopathy. Thus myositis care has to be improved. Despite the autoimmune terrain of myositis, our team has recently shown that muscle fibres themselves develop immuno-metabolic modifications that participate to muscle weakness and perpetuation of the disease1. GC effects are mediated by the glucocorticoid receptor (GR), which is expressed in various cell types including immune cells and myofibres, but the cells mediating therapeutic responses remain to be determined.Objectives:Unravel the mechanisms underlying the therapeutic effect of GC in myositis, particularly elucidate the role of skeletal muscle fibres.Methods:Experimental myositis was induced in eight to ten week-old C57BL/6J female mice by a single intradermal injection of part of skeletal muscle fast-type C protein along with Freund’s adjuvant and an intraperitoneal (IP) injection of pertussis toxin, as previously described2. Prednisone (PDN) was administered 14 days (D) after the immunization at 1 mg/kg/day for 7 days by gavage. Mice were euthanized 21 days after myositis induction. Muscle strength was assessed by grip test at D 0, before the 1st PDN administration (D 14) and the day before sacrifice (D 20). To investigate whether the PDN effects are mediated by myofibre, we generated transgenic mice carrying two LoxP sites within the GR gene in muscle, expressing the tamoxifen-inducible Cre-ERT2 recombinase selectively in skeletal muscle fibre (HSA-CreERT2/GR L2/L2). Tamoxifen (1 mg/day for 5 days by IP injection) was administered 9 days after immunization to induce GR ablation selectively in skeletal muscle fibres (GR(i)skm-/- mice). Similar treatments were applied to GR L2/L2 that do not express Cre-ER(T2), and served as controls.We compared 4 groups of myositis mice, GR L2/L2 treated by PDN (n=9) or vehicle (n=9) and GR(i)skm-/- treated by PDN (n=10) or vehicle (n=10), by grip test and at the histological level (hematoxylin-eosin (HE) and Gomori trichrome (GT) staining). Moreover, LC3 expression was studied by RTqPCR and western blot.Results:Muscle strength was decreased in both GR L2/L2 and GR(i)skm-/- myositis mice from D 14 to D 20. GR L2/L2 myositis mice recovered muscle strength after PDN treatment; no significant difference compared to D 0 was detected. In contrast, PDN did not improve muscle strength in GR(i)skm-/- myositis mice (Figure 1).HE and GT staining did not reveal quantitative differences in inflammatory infiltrate. Necrotic and degenerative fibres were detected in the 4 groups. At RTqPCR, LC3, an autophagy marker, was upregulated in PDN-treated GR L2/L2 myositis mice compared to untreated GR L2/L2 myositis mice; moreover it was 2-fold more expressed in PDN-treated GR L2/L2 myositis mice compared to PDN-treated GR(i)skm-/- mice.Conclusion:GR in skeletal muscle fibre is crucial to mediate the therapeutic response to GC in a murine model of myositis. Autophagy is one of the candidate pathways controlled by myofibre GR underlying this effect.References:[1]Meyer A et al. IFN-β-induced reactive oxygen species and mitochondrial damage contribute to muscle impairment and inflammation maintenance in dermatomyositis. Acta Neuropathol. 2017 Oct;134(4):655-666.[2]Sugihara T et al. A new murine model to define the critical pathologic and therapeutic mediators of polymyositis. Arthritis Rheum. 2007 Apr;56(4):1304-14.Disclosure of Interests:None declared

Introduction Nous avons recemment observe une prevalence elevee de myosite a inclusion dans une cohorte de patients atteints de syndrome de Sjogren (SS) primaire. La signification du SS chez les patients ayant une myosite est inconnue. L’anticorps anti 5′-nucleotidase 1A cytosolique (cN1A) a recemment ete propose comme biomarqueur de myosite a inclusion mais cet anticorps est aussi frequent chez les patients ayant un SS. Son utilite pour le diagnostic de myosite a inclusion chez les patients atteints de SS et de myosite est inconnue. Ce travail a pour objectif de decrire la signification du SS chez les patients atteints de myosites. Patients et methodes Dans cette etude monocentrique, les donnees des patients repondant aux criteres EULAR/ACR 2017 de myosite, et evalues pour le SS (criteres ACR/EULAR 2016) ont ete analysees. Quatre-vingt-dix-neuf patients ont ete inclus, couvrant l’ensemble des sous-groupes de myosite EULAR/ACR 2017, avec un suivi median de 6 ans [extremes 1,0 a 37,5]. Les 34 patients ayant une myosite avec SS (myosite/SS + ) ont ete compares aux 65 patients ayant une myosite sans SS (myosite/SS-). Resultats Une myosite a inclusion etait presente chez 24 % des patients myosite/SS+ contre 6 % du groupe myosite/SS- (p = 0,02). Aucun des patients presentant une myosite a inclusion n’a repondu au traitement immunomodulateur, qu’il soit atteint de SS ou non. L’anti-cN1A etait plus frequent chez les patients myosites/SS+ (38 % contre 6 %, p = 0,0005), independamment de la prevalence plus elevee de myosite a inclusion dans ce groupe (valeur p multivariee : 0,02). La specificite des anticorps anti-cN1A pour le diagnostic de myosite a inclusion etait de 0,96 [IC 95 %, 0,87–0,99] dans le groupe myosite SS- mais de seulement 0,70 [IC 95 %, 0,48–0,85] dans le groupe myosite/SS+. Conclusion Chez les patients atteints de myosite, la presence d’un SS est associee a une plus forte prevalence de myosite a inclusion et de l’anticorps anti-cN1A de facon independante au diagnostic de myosite a inclusion. En consequence, l’anti-cN1A a une specificite basse pour le diagnostic de myosite a inclusion chez les patients atteints de myosite avec SS associe.

Background Autoantibody detection has been assessed as tool for the diagnosis and the definition of idiopathic inflammatory myopathies (IIM). The aim of the study was to characterize the autoantibody profiling of a cohort of Italian patients with IIM. Methods Sera of 53 adult patients with definite IIM, according to Bohan–Peter criteria, were tested for anti-nuclear autoantibodies (ANA), using indirect immunofluorescence (IIF) method, and for myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs), using two new commercial immunodot assays. Results MSAs and/or MAAs were detected in 29 of 53 (54.7%) patients with IIM. Twenty-three patients (43.4%) were positive for at least one MSAs: 13 (24.5%) had anti-histidyl-tRNA synthetase autoantibodies (Jo1), 4 (7.5%) had other anti-aminoacyl-tRNA synthetases autoantibodies (anti-ARS), 1 (1.8%) had anti-transcription intermediary factor 1 gamma autoantibodies (anti-TIF1γ), 2 (3.7%) had anti-nuclear helicase protein Mi-2 autoantibodies (anti-Mi-2), 4 (7.5%) had anti-small ubiquitin like modifier activating enzyme heterodimer autoantibodies (anti-SAE). Moreover, 17 patients (32%) were positive for at least one MAAs. Coexisting MSAs and MAAs were observed in 9 of 53 (16.9%) patients, anti-Jo1/SS-A autoantibodies in most cases. Overall sensitivity of immunodot assays was 54.7%, the specificity was almost absolute. At cut-off value of 1:160, the sensitivity of ANA-IIF was 52.8%, increasing to 66% if cytoplasmatic fluorescence reaction was reported. Notably, two (5.7%) ANA-IIF negative patients had MSAs, detected only by immunodot assays. Conclusion It was possible to identify MSAs otherwise undetectable because of the use of new assays. Immunodot can reveal MSAs even when IIF results are inconclusive or, in some cases, ANA negative.

Background:Dermatomyositis (DM) shows a wide clinical spectrum that seems to be different based on the type of autoantibody status. Furthermore, less is known regarding to the histopathology of different serological subsets of DMObjectives:The aim of our study was to investigate clinical and histopathological hallmarks in adult DM patients positive for anti-Mi2 (Mi2+) antibody compared to DM patients negative for anti-Mi2 (Mi2-)Methods:All clinical data of adult DM patients admitted in three tertiary Rheumatology Units, who fulfilled EULAR/ACR 2017 classification criteria1, were included in this study. Overlap syndrome and antisynthetase syndrome were exclusion criterion. Serum samples were tested in the local reference laboratories using line immunoassays methods for Myositis specific and associated antibodies. Histopathological study was carried out from muscle biopsies performed for diagnostic purpose in outpatient clinic of Bari (Italy) University. Quantitative analysis was performed for myofiber and capillary features, whereas semi-quantitative analysis (score from 0 to 3) was performed for inflammatory cells infiltrate, both at endomysial and perimysial sitesResults:A total of 95 DM patients, followed for a median (IQR) follow-up of 28 (9-85) months, were analyzed. Of these, 23 (24.2%) patients (87% female, mean age at onset 55.4±16.2 years) were anti-Mi2+, while 72 (75.8%) patients were Mi2- (72.2% female, mean age at onset 55.2±17 years). All Mi2+ patients showed muscle involvement. Moreover, Mi2+ DM showed higher levels of serum creatine kinase (CK) at onset compared to Mi2- (CK (IQR): 2649 UI/l (1130-6000) vs 575 UI/l (164-1617), pConclusion:Mi2+ patients represent a specific DM subset with higher muscle damage, sarcoplasmic MAC deposits and endomysial macrophages infiltration as histological hallmarksReferences:[1]Ann Rheum Dis. 2017 Dec;76(12):1955-1964Disclosure of Interests:Marco Fornaro: None declared, Francesco Girolamo: None declared, Lorenzo Cavagna: None declared, Franco Franceschini: None declared, margherita giannini: None declared, Giovanni Zanframundo: None declared, Micaela Fredi: None declared, Marilin Tampoia: None declared, Angela Amati: None declared, Luigi Serlenga: None declared, Anna Lia: None declared, Liala Moschetti: None declared, Dario Dabbicco: None declared, Laura Coladonato: None declared, Florenzo Iannone Consultant of: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Speakers bureau: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD

Background Anti-MDA5 antibodies are a known set of antibodies observed mainly in dermatomyositis, typically associated with cutaneous involvement, presence and often rapid progression (RP) of interstitial lung disease (ILD) and amyopathic muscle involvement. Despite the increased attention, described cohorts involves only a limited number of cases Objectives to define clinical characteristics of a large cohort of anti-MDA5 antibodies positive patients Methods Retrospective assessment of anti-MDA5 positive patients from centres referring to our group Results 82 anti-MDA5 positive cases (56 females) were collected. In median: onset age was 44 Y (IQR 22.57), diagnostic delay 4 Mo (IQR 1–10), follow-up 13 Mo (IQR 3–43). Fifty-three patients had ILD, that was RP in 24 cases (15 at ILD onset, 9 after ILD onset). Fifthteen ILD patients were admitted in Intensive Care Unit (ICU): 4 were treated with Extracorporeal-Membrane-Oxygenation, 7 with mechanical-invasive and 2 with mechanical-non-invasive ventilation. Forthy-nine patients had muscle involvement (39 symptomatic), 42 arthritis, 54 cutaneous involvement, 9 history of malignancy. Twelve patients died (ILD=7, ILD and sepsis=3, neoplasia=1, not specified=1), 7 of those in ICU Conclusions In our cohort, ILD was the most frequent finding. A RP of ILD was common, occurring also in ILD with symptomatic/chronic onset. The low rate of survival in ICU raised the problem of follow up and early treatment of ILD. In our cohort arthritis was common and muscle involvement mainly symptomatic. Finally, the high percentage of observed malignancies suggests a careful neoplastic screening and follow up Reference [1] Labrador-Horrillo M, et al. J Immunol Res2014;2014:290797. Disclosure of Interest None declared

Background Antisynthetase syndrome (ASSD) is an autoimmune disease characterised by the clinical triad arthritis, myositis, and interstitial lung disease (ILD). Despite Raynaud’s phenomenon (RP) is another typical feature of ASSD, nailfold videocapillaroscopy (NVC) assessment of these patients has been only sporadically described, without the elucidating data for clinicians. Objectives To describe NVC features of ASSD patients and to investigate possible correlations with clinical and serological features of the disease. Methods We retrospectively analysed NVC images of 190 ASSD patients (females/males 3.76, mean age 49.7±12.8 years, mean disease duration 51.2±71.4 months, 133 anti-Jo-1 and 57 non-anti-Jo-1 positive patients). For each patient, we examined number of capillaries, giant capillaries, micro-haemorrhages, avascular areas, ramified capillaries, and the presence of scleroderma (SSc) patterns. Finally, we correlated NVC features with clinical and serological findings of ASSD patients. Results NVC abnormalities were observed in 62.1% of AASD patients compared with 29.3% of a group of 75 patients with primary Raynaud’s phenomenon (p Conclusions NVC abnormalities are commonly observed in ASSD, independently to the occurrence of RP. The presence of a SSc-like pattern should let to identify a more defined ASSD subtype and prospective studies could confirm the association with clinical and serological features of ASSD. Disclosure of Interest None declared

Background Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disorder mainly characterised by persistent high spiking fevers, evanescent rash, and joint involvement. Data on the efficacy of biologic therapy in the management of AOSD1 is increasing and represents a breakthrough in the management of patients with AOSD refractory to corticosteroids (CS) or conventional (c) DMARDs. Objectives We aimed to evaluate possible predictor on the need to use a biologic agent in the management of AOSD patients. Methods In this retrospective monocentric study we evaluated AOSD patients followed in our outpatient’s clinic since 2010 with at least 1 year follow-up. Clinical manifestations, joint involvement, CS and c- or bDMARD use were main outcome measures. T-test or ANOVA and Chi-squared were used to compare continuous or categorial data, when appropriate, and the odds ratio (OR) for which condition had an influence on clinical outcome was calculated. Results We evaluated 28 AOSD patients (mean age 43±14 years; median disease duration 3 (95%CI 2.5–17.3) months). All patients at baseline were treated with a median CS of 18.7 (95%CI 14.3–24.8) mg/die prednisone equivalent dose, and median methotrexate (MTX) dose of 15 (95%CI 13.4–16.28) mg/week. After 1 year follow-up, in the 8 patients (28.6%) that needed to start a bDMARD (4 anti-IL1; 3 anti-IL6 and 1 anti-TNF), we observed that baseline joint involvement was the more prevalent manifestation of the disease with higher DAS28 compared to those patients still on CS +MTX (DAS28 3.8±1.2 vs 2.8±1.1, respectively p=0.03). Moreover, we showed that clinical manifestations of systemic involvement (i.e. fever, rash, organomegaly and anaemia) were associated with a protective risk to start a bDMARD at 1 year (OR 0.4 95% CI 0.2–0.76). Consistently, in those patients with concomitant elevated ESR (>20 mm/h), CRP (>15 mg/L) and ferritin (>250 ng/ml) levels at baseline, we observed a low risk to start a bDMARD at 1 year follow-up (OR 0.4 95% CI 0.18–0.87). Conclusions In our cohort about one third of AOSD patients required to be treated with a bDMARD at 1 year follow-up, mainly if joint involvement was the predominant clinical manifestation at disease onset. Systemic manifestations of the disease seem to benefit from high dose CS+MTX combination therapy. Further studies with more extensive cases are necessary. Reference [1] Cavalli G, Franchini S, Aiello P, Guglielmi B, Berti A, Campochiaro C, Sabbadini MG, Baldissera E, Dagna L. Efficacy and safety of biological agents in adult-onset Still’s disease. Scand J Rheumatol2015;44(4):309–14. Disclosure of Interest None declared

Background Immune mediated necrotizing myopathy (IMNM) is a recently recognised pathology within the spectrum of idiopathic inflammatory myopathies (IIMs). Specific autoantibodies and the response to immunosuppressants aid to make the diagnosis and suggest immune-mediated pathogenesis, although histopathological features are not specific for IMNM. Autophagy and ubiquitin-proteasome system are two interacting systems by which dysfunctional cellular components are degraded in the cell. Their dysregulation, in sporadic Inclusion Body Myositis (sIBM), seems to be responsible for the protein aggregates. The autophagy dysfunction in IMNM was not widely investigated. Objectives To investigate autophagy marker expression, macrophages localization and accumulation of misfolded proteins in non-necrotic fibres of IMNM muscle in comparison with Dermatomyositis (DM), Polymyositis (PM) and sIBM. Methods Among 52 IIMs diagnosed from January 2015 to June 2017, we reviewed muscle biopsies and stored sera. Six subjects were included in the IMNM group, characterised by many necrotic muscle fibres, regenerating muscle fibres and no significant inflammation despite of numerous but scattered macrophages removing necrotic muscle fibres. Two patients had anti-signal recognition particle (SRP) autoantibodies, two patients anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), the others tested negative for specific autoantibodies. All IMNM patients had a positive response to immunosuppressants. Muscle sections were immunolabelled with the following antigens: ubiquitin, autophagy markers LC3b, p62 (a receptor of autophagy), TDP-43 (a marker of ubiquitinated proteic inclusions), SMI31 and SMI310 (Phosphorylated Neurofilaments), CD31 (endothelial cell marker), C5b-9 (membrane attack complex), CD4 (T-helper lymphocytes), CD8 (T-suppressor lymphocytes), CD68 (macrophages), CD20 (B-lymphocytes), CD56 (NK lymphocytes and regenerating muscle fibres), MHC I, MHC II. Quantitative results were compared among IMNM (n=6), DM (n=4), sIBM (n=4), PM (n=5) and healthy controls (n=4). Results In IMNM, inflammation was mild compared with DM, PM, sIBM, and consisted in sporadic endomysial and/or perivascular cells CD68+. Skeletal muscle fibres (SMFs) containing LC3b+puncta were significantly higher in IMNM and IBMs than in DM or PM. In all IMNM, the greater proportion of LC3b+puncta was localised in CD56 +fibres (figure 1), instead, sIBM showed a high number of LC3b+puncta in vacuolated SMFs with low expression of CD56 +SMFs. As expected, P62 and SMI31 aggregates were significantly higher in sIBM than in the other IIMs, even if, also in IMNM, there were moderate p62 accumulations and a little proportion of SMFs stained by SMI31. Finally, in IMNM there was the highest number of ubiquitin +SMFs. Conclusions These findings suggest an involvement of cellular clearance systems in the pathophysiology of IMNM similarly to sIBM. Nevertheless, LC3b+puncta in regenerating fibres can be considered a peculiar biomarker in IMNM. Further studies of larger cohort of patients are needed to better define IMNM. Disclosure of Interest None declared

Background The lung is the most frequently involved extramuscular organ in idiopathic inflammatory myopathies (IIMs); the most common form of lung involvement is interstitial lung disease (ILD). Some autoantibodies are strongly associated with ILD and with specific phenotypes and prognosis of ILD. Among myositis-specific auto-antibodies (MSAs), antibodies against aminoacyl-tRNA-synthetases (AsAb) are the strongest predictive factors for ILD, and anti-Jo-1 is the most common AsAb. Among myositis-associated auto-antibodies (MAAs), anti-SSA/Ro52 is frequently found in sera of patients with IIM and ILD, often associated with anti-Jo-1. The coexistence of anti-SSA/Ro52 and anti Jo-1 seems to be related to a more severe and extensive pulmonary fibrosis with higher score in HRCT compared with the patients with only anti-Jo-1 antibodies. Furthermore, some reports suggest that presence of anti-Jo-1 could be a biomarker for good prognosis 1 . The significance of antibodies levels for the prognosis of ILD in IIMs was not widely investigated. Objectives To investigate the relationship between antibody levels and clinical manifestations, laboratory data, pulmonary function tests (PFTs), disease activity indices in ILD associated to IIMs. Methods Among 130 IIMs admitted to Rheumatology Unit of Bari from January 2010 to January 2018, we retrospectively examined 49 patients (40 F; 22 PM, 25 DM, 1 IBM; mean age at ILD onset 51 years, range: 23–83) because of ILD defined by high resolution computed tomography (HRCT). Clinical manifestations, laboratory data, HRCT pattern, PFTs (FVC, FEV1 and DLCO), therapy, disease activity as Manual Muscle Test (MMT-12), Health Assessment Questionnaire (HAQ), Physician Global Assessment (PGA) at ILD onset, were obtained from medical records. Ferritin levels and autoantibodies were detected in serum samples collected at ILD onset. ANA were tested by IIF on HEp-2 cell substrates, MSAs (JO1, EJO, OJ, PL7, PL12, SRP, HMGCR, Mi2, TIF1γ, MDA5, NXP2, SAE) and MAAs (Ro52, Ku, PM/Scl 75–100, RNP, Scl70) by line-blot method. Anti-SSA and anti-Jo1 were also detected by CLIA method. Correlation analysis were run using parametric and non-parametric test according to data distribution. Results 45 of 49 (91,8%) patients were positive for MSAs and/or MAAs. 40 of 45 (88%) were positive at least one of MSAs. The double presence of MSAs and anti-Ro52 was observed in 21 of 40 (52,5%), showing anti-Jo1/SSA in most cases (15/21, 71,4%). Among all correlations studied between anti-Jo1 or anti-SSA levels and PGA or PFTs, we found a significantly correlation between anti-Jo1 and PGA (p=0,03, R=0,46). We didn’t find significantly correlation between autoantibodies and ferritin serum levels. Conclusions These findigs confirm that ILD was associated with autoantibodies positivity. Further studies in larger cohort need to investigate if autoantibodies levels have a prognostic role in global outcome. Unlikely some controversial works in literature, serum ferritin does not seem a biomarker of severity of lung involvement in IIMs. Reference [1] Labirua A, et al. Interstitial lung disease and idiopathic inflammatory myopathies: progress and pitfalls. Curr Opin Rheumatol2010. Disclosure of Interest None declared

Background Polymyositis (PM) and Dermatomyositis (DM) are systemic inflammatory diseases affecting skeletal muscles and other organs, particularly hypopharynx and the upper tract of the esophagus, causing motility dysfunction. The current treatment for PM and DM relies on steroids and immunosuppressants, but esophageal involvement is often refractory to standard therapies. Objectives To assess the efficacy and safety of intravenous immunoglobulins (Ig-iv) as therapy of refractory dysphagia (1) in patients affected with PM/DM who have received conventional treatments for at least three months. These are the extended data of a previous abstract entitled “Improvement of refractory dysphagia in patients with idiopathic inflammatory myopathies receiving immunoglobulin intravenous therapy” accepted to EULAR 2015 Congress. Methods We enrolled 17 patients (15 F), 8 with DM, 9 with PM according to Bohan and Peter criteria, treated with prednisone (mean dose 20 mg/day) ± Methotrexate (15 mg/wk) or Azathioprine (100 mg/day) for at least 3 months, without improvement of dysphagia. All patients received one infusion of Ig at a standard dose (2 g/kg in a day) every two months for 3 cycles. In all patients, at entry and before each infusion, creatine kinase (CK) levels and Manual Muscle strength Test on 12 muscle groups (MMT12) were evaluated. Dysphagia assessment included: Eating Assessment Tool (EAT) impaired for score ≥3; Three-oz Swallow Test (3oST) and fibrolaryngoscopy (FEES) for pharyngeal muscle propulsion and stasis of liquid/solid bolus detection. Student T-test and Chi-square test were used to compare baseline and follow-up data. Results At entry, all patients had an EAT score ≥3 with a mean score of 16.2±9, 3 patients presented a 3oST for solid (STPNS) impaired, and only 1 patient also for liquid (STPNL). CK levels were slightly increased (474±720 UI/L), and MMT12 score was 4.45±0.35. Following Ig-iv therapy we observed a significant improvement of EAT score after the first dose (9±8, p=0.006) with a further reduction after the second dose (7.4±8, p=0.007) and stability after the third one (7.6±8, p=0.008). An improvement of pharyngeal muscle propulsion, with a significant resolution of solid stasis and a partial resolution of liquid stasis were observed. In addition, MMT12 score progressively improved after each dose, increasing at 4.86±0.16 after the third dose (p=0.001). Noteworthy, after the third Ig-iv dose, three patients stopped the steroid and the remaining 12 were treated with a significant lower dose of 5 mg/day of prednisone (p=0.04). Conclusions According to literature, our findings provided evidence that Ig-iv induced a meaningful improvement of dysphagia, also having a steroid-sparing effect. An improvement of muscle strength was also detected. Although further studies of larger cohort of patients and a longer follow-up time are needed, our findings corroborate the utility of Ig-iv in the treatment of more resistant idiopathic inflammatory myositis related dysphagia. References Marie I et al. Intravenous immunoglobulins for steroid-refractory esophageal involvement related to polymyositis and dermatomyositis: a series of 73 patients. Arthritis Care Res. 2010;62(12). Disclosure of Interest None declared

Background Adipose tissue (AT) is an endocrine organ able to secrete the “adipokine” molecules that contribute to the low-grade inflammatory state in obese subjects and to the local inflammation that affects joints and bone (1,2). High-grade inflammation, in course of RA, leads to an altered body composition (3,4), characterized by the increasing of fat mass and the decreasing of lean mass, mostly not associated to body mass index (BMI) variations (3,5). The BMI is not able to differentiate visceral (VTH) and subcutaneous (STH) fat tissue and to distinguish between muscle mass and fat mass body composition (BC) (6,7). Alternative methods proposed for assessment of visceral fat deposition, are bioelectrical impedance analysis (BIA) and ultrasonography (US). Objectives The aim of the study is to investigate if BC, assessed by BIA and US, correlates with disease activity (assessed by the Disease Activity Score using 28 joint counts – DAS28) and affects the response to the therapy (DAS 28 variation from first evaluation). Methods 87 consecutive RA patients (pts) (72 women and 15 men; aged 52.4±13.2 years; disease duration of 10.7±8.6 years), treated with DMARDs and/or biologics (bDMARDs), were recruited during their regular visit. The inclusion criteria were the 1987 American College of Rheumatology (ACR) or ACR/EULAR 2010 classification criteria. The pts underwent to anthropometric measures (BMI); abdominal US to assess STH and VTH and derived computing of peritoneal circumference (PC); and BIA to the indices of body composition (fat-free mass index (FFMI) and fat mass index (FMI). Results We observed increasing values of BMI, FMI, VTH (fig. 1) and CP with the worsening of disease activity phases, evaluated by DAS 28. In particular, pts with DAS28≥5.1 had highest BMI (30,9±2; p=0,036), FMI (11,5±1,6; p=0,05), CP (92,7±12,5 cm; p=0,035) and VTH (24,8±5,8 mm; p=0,046) than pts in less severe disease activity. By linear regression analysis the predictor of higher DAS28 is the BMI (p=0,028). As regard the drug response, the predictors of DAS 28 improvement are higher FFMI (p=0,044) and lower BMI (p=0,015), independently by bDMARDs or DMARDs treatment. A trend to higher FMI and US AT measures was observed in female with high disease activity, in particular in menopause pts. Conclusions An altered fat distribution is observed in active RA phases; in particular, the FMI increasing is attributable just to visceral AT (VTH and CP). An inflammatory hyperactivity of visceral adiposity could be supposed in RA. The body composition, in addition to BMI, seems to predict the disease activity and drug response in RA patients. The evaluation of VTH by US could be useful to not overestimate the disease activity; instead the BIA could be a useful tool to support the clinicians in a more aggressive treatment management. References Nat Clin Pract Rheumatol 2007; 3(12):716–24. J Mol Endocrinol 2009; 43(1):11–8. Mediators Inflamm 2013; 2013:710928. Arthritis Care Res (Hoboken) 2012; 64(10):1471–9. Nat Rev Rheumatol 2010; 6(8):445–51. Curr Opin Clin Nutr Metab Care 2003; 6(4):387–93. Ann Rheum Dis 2007; 66(10):1316–21. Disclosure of Interest None declared

Background Rheumatoid arthritis (RA) patients have an increased mortality for cardiovascular (CV) events, not completely explained by impaired cholesterol levels or other traditional CV risk factor (1). Target therapy with effective control of systemic inflammation have been demonstrated to improve articular outcomes, but the effect on CV risk is still under investigation (2). The ability of high-density lipoprotein (HDL) to accept cholesterol from macrophages (HDL cholesterol efflux capacity; HDLc-EC) is a key step in reverse cholesterol transport, with significant consequences on incident atherosclerotic CV disease (3), but this marker in RA have still alternate evidence (4,5). Objectives To assess the effects of different biological DMARDs on HDLc-EC in RA Methods Disease activity data and blood samples from 40 patients with RA before and up to 12 months after starting a biologic therapy were collected. The study included patients starting intravenously administered Abatacept (ABA;n=10), Infliximab (INF;n=10), Tocilizumab (TCZ;n=10), and Rituximab (RTX;n=10), at approved dose regimens for RA treatment. HDLc-EC was measured on paired serum samples using THP-1 macrophages and a fluorometric assay for cholesterol measurement. ANOVA was used to compare paired continuous data, and Pearson9 r value was calculated for correlations. Results Disease activity assessed by DAS28-CRP and CDAI significantly dropped during all treatments. No significant changes in total and high or light density cholesterol fractions were detected. HDLc-EC at baseline was 22±3% with a statistically significant increase up to 25±3% and 27±4% after 6 and 12 months of treatment, respectively (P Conclusions Biologic treatment can influence the HDLc-EC of RA patients, already after 6 months of therapy, and is associated with changes in disease activity and inflammatory status. Infliximab and Rituximab seem to have an enhanced impact on HDLc-EC. Future studies need to address the mechanisms beyond these intriguing findings. References Arts EE et al. Ann Rheum Dis. 2015;74:998–1003. Woodworth TG, den Broeder AA. Best Pract Res Clin Rheumatol. 2015;29:543–9. Rohatgi A. et al. N Engl J Med 2014;371:2383–93. Liao KP et al. J Am Heart Assoc. 2015;4(2). Ormseth MJ. et al. Arthritis Rheumatol. 2016;68:2099–105. Disclosure of Interest None declared

Auto-antibodies against aminoacyl-tRNA-synthetases (anti-ARS Abs) represent the hallmark of the anti-synthetase syndrome that is defined as the clinical association of fever, Raynaud's phenomenon, myositis, interstitial lung disease (ILD), arthritis and mechanic's hands. Recently, differences in clinical features depending on specific anti-ARS Abs have been reported. We describe three cases of anti-EJ (anti-glycyl) antibody-positive patients presenting with ILD as a common feature, but with heterogeneous histopathological and radiographic patterns and with different responses to treatment. Relapsing-remittent fever, refractory muscle involvement and seronegative arthritis were also striking clinical manifestations.

Among the idiopathic inflammatory myopathies, anti-synthetase syndrome (ASS) and inclusion body myositis (IBM) have distinctive clinical profiles: fever, Raynaud’s phenomenon (RP), interstitial lun...

BACKGROUND: Autoantibody detection has been assessed as tool for the diagnosis and the definition of idiopathic inflammatory myopathies (IIM). The aim of the study was to characterize the autoantibody profiling of a cohort of Italian patients with IIM. METHODS: Sera of 53 adult patients with definite IIM, according to Bohan–Peter criteria, were tested for anti‐nuclear autoantibodies (ANA), using indirect immunofluorescence (IIF) method, and for myositis‐specific autoantibodies (MSAs) and myositis‐associated autoantibodies (MAAs), using two new commercial immunodot assays. RESULTS: MSAs and/or MAAs were detected in 29 of 53 (54.7%) patients with IIM. Twenty‐three patients (43.4%) were positive for at least one MSAs: 13 (24.5%) had anti‐histidyl‐tRNA synthetase autoantibodies (Jo1), 4 (7.5%) had other anti‐aminoacyl‐tRNA synthetases autoantibodies (anti‐ARS), 1 (1.8%) had anti‐transcription intermediary factor 1 gamma autoantibodies (anti‐TIF1γ), 2 (3.7%) had anti‐nuclear helicase protein Mi‐2 autoantibodies (anti‐Mi‐2), 4 (7.5%) had anti‐small ubiquitin like modifier activating enzyme heterodimer autoantibodies (anti‐SAE). Moreover, 17 patients (32%) were positive for at least one MAAs. Coexisting MSAs and MAAs were observed in 9 of 53 (16.9%) patients, anti‐Jo1/SS‐A autoantibodies in most cases. Overall sensitivity of immunodot assays was 54.7%, the specificity was almost absolute. At cut‐off value of 1:160, the sensitivity of ANA‐IIF was 52.8%, increasing to 66% if cytoplasmatic fluorescence reaction was reported. Notably, two (5.7%) ANA‐IIF negative patients had MSAs, detected only by immunodot assays. CONCLUSION: It was possible to identify MSAs otherwise undetectable because of the use of new assays. Immunodot can reveal MSAs even when IIF results are inconclusive or, in some cases, ANA negative.

Background The clinical phenotype of the antisynthetase syndrome (AS) has been related with the underlying autoantibody specificity. The typical disease triad (arthritis, myositis, and interstitial lung disease -ILD) is common in anti Jo-1 + AS, whereas isolated ILD is associated with anti PL-7 and PL-12 Ab. The majority of anti Jo-1 + patients without all triad findings at the onset (incomplete ASSD) will develop lacking features during the followup Objectives To assess the triad clinical spectrum time course in non anti Jo-1 + AS Methods The study cohort included patients + for anti-EJ, OJ, PL-7, or PL-12 Ab with at least 1 triad finding. Clinical features were retrospectively collected and analyzed Results we included 65 non anti Jo-1 + AS (7 anti EJ, 4 anti OJ, 30 anti PL-12, 24 anti PL-7; 49 females, 16 males). In median, age at disease onset was 53 years (IQR 42–64), diagnostic delay 9 months (IQR 3–23.5), followup 60 months (IQR 20.5–113). Patients9 characteristics are reported in Table 1. During the followup, 22/61 patients with incomplete AS developed new triad findings, in median 12 months (IQR 6–27) after disease onset. The frequency of incomplete AS developing new triad findings and the length of followup were significantly reduced in non anti Jo-1 + patients with respect to our corresponding anti Jo-1 + cohort (respectively: 22/61 vs 138/220, p Conclusions In non anti Jo-1 + patients the ex novo occurrence of classic triad finding is common, but less frequent than in anti Jo-1 + patients. The different length of followup may explain at least partly this difference References Cavagna L, et al. Medicine (Baltimore) 2015;94:e1144 Disclosure of Interest None declared

Background Interstitial lung disease (ILD) is a typical clinical manifestation in Systemic Sclerosis (SSc). The high resolution chest computed tomography (HRCT) is the gold standard to evaluate and grade ILD. The presence of fibrotic tissue in the lung, or other structures beside the air, allows obtaining specific sonography images (such as ultrasound lung comet, higher pleural line thickness, irregular pleural margins and subpleural cysts) by chest ultrasound. In previous studies it was demonstrated that the ultrasound comets number increases in SSc patients. Objectives We aimed at correlating the specific lung sonography signs with ground glass and honeycombing pattern detected by chest HRCT. Methods A total of 60 SSc outpatients (54 female, mean age 56,2 ± 13,8 ys and disease duration of 9,57±8,7 ys), who fulfilled ACR/EULAR 2013 SSc classification criteria, were recruited. All patients underwent chest HRCT and US examination. The US examination was performed with 7,5 Mhz probe and conducted with patients in sitting position from paraspinal line to anterior axillary line, for each intercostals space. The presence of typical ultrasound signs as lung comets (pathological if >35), higher pleural line thickness (pathological if >2mm), irregular pleural margins, subpleural cysts and pleural effusion was detected. The sensitivity, specificity and accuracy of US patterns (compared to chest HRTC) were evaluated by ROC analysis. Statistic significance was set at p Results 23 patients had the CT honeycombing pattern, of which 92% had the US irregular pleural margins, 70% had US higher pleural line thickness and sub-pleural cysts, just 54% had US lung comets. 16 patients had the CT ground glass pattern, of these in 94% the US irregular pleural margins, in 87% US lung comets, in 60% US higher pleural line thickness were found. As regard the CT ground glass pattern the US sign with the highest specificity (91%), sensibility (85,7%) and accuracy (88%) was the lung comets; while regarding the CT honeycombing pattern the US sign with the highest specificity (92%), sensibility (69,6%) and accuracy (82%). Conclusions The lung US is a good diagnostic technique for its repeatability, low cost and risklessness. Although HRCT remains the best imaging technique to assess the ILD, in SSC the lung US could be a useful tool to detect the presence or the evolution of ILD and to improve the timing of HRTC without exposing the patients to high radiation doses over time. Disclosure of Interest None declared

Background Systemic sclerosis (SSc) is a connective disease characterized by severe microvessels vasculopathy. The important role of endothelial dysfunction in SSc pathogenesis is widely demonstrated, but the SSc related autonomic nervous system impairment is controversial and rarely described. The dysregulation of axon reflex vasodilatation of fingertip microvessels in SSc has been reported in some studies, but the functional involvement of digital arteries in SSc patients had never been investigated. Objectives We aimed at evaluating the blood flux changes mediated by axon reflex response upon heating stimulus in SSc patients. Methods 87 SSc patients (SSc pt) and 22 healthy controls (HC) were recruited in this study. The SSc patients were aged 52,7±16,2 yrs, with disease duration of 8,23±7,8 yrs. The LD Flowmetry (Periflux System 5000, Perimed) with 4 LD heating probes was used to measure the skin blood flux of the middle phalanx of the 2nd, 3rd, 4th and 5th fingers of the left hand. The skin fingers flux was recorded at pre-heating period with probes temperature fixed at 34 °C (PHF) and after 5 min heating at 44 °C (IHF). Therefore, the heating test assesses the variation of digital artery flux in response to local heating stress at 44 °C. The ratio IHF/PHF evaluates the axon reflex mediated vasodilatation (ARMV). The results are expressed as average across 4 fingers at each time. The flux was expressed in perfusion unit (PU) and HC and SSc patients responses were compared by the t-student test. Statistic significance was set at p≤0,05. The data analysis was performed using IBM SPSS statistic 20. Results The ARMV was significantly reduced in SSc patients (2,2±1,4) in comparison with HC (4,8±2,7, p=0,0001). IHF was lower in SSc patients (118,6±54,3) than HC (168±78, p=0,001). Dividing the SSc pts group by the presence of pitting scars (PS), digital ulcers (DU) and digital necrosis (DN), we observed a lower IHF in SSc pts with PS (103,2±48,6) than in SSc pts without (138,1±56, p=0,003), and in SSc pts with DU (97,8±47,6) than in SSc pts without (160,27±120,1, p=0,002). Moreover, SSc pts with ND showed a lower ARMV (1,8±1) than SSc pts without (2,6±1,5, p=0,006), and a lower IHF (98,3±49,1 vs 133,2±54,5, p=0,004). The age, sex, concomitant therapy with Ca-antagonist or Bosentan or cardioaspirin did not influence the digital artery flux. Conclusions This study provided evidence that a functional impairment of DA occurs in SSc, and it worsens with increasing severity of vascular clinical manifestations. Disclosure of Interest None declared

Background Articular involvement is reported to occur in up to 85% of patients with antisynthetase syndrome (ASSD) and it may be the only onset feature, although with frequencies and characteristics not still defined Objectives To determine in a large international cohort of anti Jo-1 positive ASSD the prevalence of isolated arthritis at disease onset. To describe the clinical, serological and radiological characteristics and evolution of these patients Methods We included all anti Jo-1 positive patients referring to participating centres and with an isolated arthritis at disease onset. The pattern of articular involvement, radiological and serological characteristics of patients were analysed. IgM-Rheumatoid factor (RF) was assessed by immunonephelometry; anti-cyclic citrullinated peptide antibodies (ACPA) by commercial second-generation ELISA kits; anti Jo-1 and anti-Ro positivity by commercially available ELISA kits Results An isolated arthritis was the first manifestation in 54 (41 females, 13 males) out of the 225 patients included (167 females, 58 males), with a prevalence of 24%. Main characteristics of arthritis and overal results has been completely reported in table 1. Conclusions We confirmed that an isolated polyarthritis is the first symptom of anti Jo-1 positive ASSD in up to a quarter of cases. Arthritis is mainly polyarticular and symmetrical, and the positivity for IgM RF or ACPA or both is not a rare finding, as well as the occurrence of marginal X-rays joint erosions. Anti-Ro positivity and RP occurrence may help clinician in the early identification of ASSD, even if the high rate of subsequent appearance of ILD and myositis clearly suggest that the screening for an underlying ASSD should be performed also in patients that may be undoubtedly diagnosed with RA. References Cavagna L, et al. Characterization of anti Jo-1 positive antisynthetase syndrome: results from an international multicentre study. Arthritis Rheum 2014;11:S550. Lefevre G, et al. Seronegative polyarthritis revealing antisynthetase syndrome: a multicentre study of 40 patients. Rheumatology (Oxford). 2014 Oct 27. pii:keu404. [Epub ahead of print] Disclosure of Interest None declared

Background Behcet9s disease (BD) is a multi-systemic disorder of unknown aetiology characterized by relapsing oral–genital ulcers, uveitis, and involvement of vascular, gastrointestinal, neurological and musculoskeletal system. Although disease pathogenesis is still unclear, the main actors seem to be genetic background and activation of both innate and adaptive immunity ensuing in an interaction between T lymphocytes and neutrophils. Indeed, multiple pro-inflammatory cytokines are involved in different pathogenic pathways that eventually lead to tissue damage in BD. Objectives The aims of our study were to evaluate serum cytokines levels of IL-8, IL-18, IFN-α2a, IL-6, IFN-γ, CXCL10, CXCL11, CXCL9 and SAA levels in patients with BD, in comparison to healthy controls (HC), and to correlate their levels to disease activity. Methods The study included 78 serum samples obtained from 58 BD patients. We analysed a set of pro-inflammatory cytokines including IL-8, IL-18, IFN-α2a, IL-6, IFN-γ, CXCL10, CXCL11 and CXCL9 by multiplex bead analysis as well as SAA by ELISA. Results Compared to HC, BD patients showed elevated cytokine levels of IL-8 (p=0.0001), IL-18 (p=0.0058), IFN-α2a (p=0.0181) and IL-6 (p=0.0233), and low levels of CXCL11 ( p =0.0369) (Table 1). When BD patients were divided into active and inactive group, we observed enhanced IL-8 and IL-18 in both groups compared to HC, while IFN-α2a ( p =0.0141) and IL-6 ( p =0.0332) were raised in active group compared to HC. Moreover, CXCL11 ( p =0.0154) serum concentrations were significantly lower in inactive-BD than HC (Table 1). In the second part of the study, we compared serum cytokine profiles between BD patients with SAA serum levels ≤20 mg/L (negative-SAA), >20 mg/L (positive-SAA) and HC. Interestingly, we observed that positive-SAA BD patients showed higher levels of inflammatory markers than HC or negative-SAA group. Among these cytokines, IL-18, IFN-α2a and IL-6 were higher in positive-SAA BD group than HC whilst IL-8 and CXCL9 levels were higher than in negative-SAA and HC (Table 1). Conclusions BD patients exhibited elevated levels of inflammatory mediators, more evident in active disease and positive-SAA group, suggesting that may exist a relationship between SAA and pro-inflammatory cytokines in the intricate scenario of BD pathogenesis. References Hatemi G, Yazici Y, Yazici H. Behcet9s syndrome. Rheum Dis Clin North Am 2013; 39:245–61. Hamzaoui K, Hamzaoui M, Guemira F, Bessioud M, Hamza M & Ayed K. (2002) Cytokine profile in Behcet9s disease patients. Relationship with disease activity. Scand J Rheumatol 31: 205-10. Uhlar CM, Whitehead AS. Serum amyloid A, the major vertebrate acute-phase reactant. Eur J Biochem. 1999 Oct;265(2):501-23. Nara K, Kurokawa MS, Chiba S et al. Involvement of innate immunity in the pathogenesis of intestinal Behcet9s disease. Clin Exp Immunol 2008;152:24551. Disclosure of Interest None declared