Search

Background:Myositis-specific antibodies (MSA) are highly specific and useful to classify patients as having syndromes with distinct clinical features and prognosis. MSA are almost always mutually exclusive and quite specific, adding value as a useful biomarker for diagnosis. Although individual autoantibodies aren’t sensitive enough to detect the full spectrum of idiopathic inflammatory myopathies (IIM), the sensitivity of a myositis panel is increasing as more autoantibodies are discovered, and as better assays become available.Objectives:We aimed to analyze the usefulness of a myositis-specific immunoblot for the diagnosis of IIM in a hospital cohort from January 2019 to December 2020. We also seek to correlate immunological findings with the risk of associated interstitial lung disease (ILD), cancer, or death.Methods:Retrospective single-center observational study conducted in a Spanish tertiary hospital. In patients with high clinical suspicion of IIM, a myositis immunoblot was performed including Jo1, PL-7, PL-12, EJ, SRP, Mi2, Ku, MDA-5, TIF1-γ, HMGCR, PM-Scl and Ro52 antibodies. The demographic characteristics, the risk of ILD, cancer and death were analyzed.Results:In a cohort of 313 patients with high suspicion of IIM, 87 patients (27.8%) presented a positive MSA (MSA+ve). The mean age at diagnosis was 56.7±16.9 years, with no significant differences between MSA+ve and MSA-ve (p=0.597). Most of the patients were women with significant differences between both groups (80.5% MSA+ve vs 68.1% MSA-ve, p=0.030).IIM were classified as antisynthetase syndrome (ARS) (38%), dermatomyositis (DM) (31%), overlap myopathy (OM) (16.9%) and necrotizing myopathy (NM) (14.1%) according to the manifestations and MSA found (Jo1, PL-12, PL-7, EJ in ARS; Mi-2, MDA-5 and TIF1-γ in DM; Ku and PM-Scl in OM; HMGCR and SRP in NM). The most frequent MSA were anti-Jo1 (16.9%), TIF1-γ (15.5%), Ku (12.7%), Mi-2 (9.9%), PL-7 (9.9%), HMCGR (8.5%), PL-12 (7%), MDA-5 (5.6%), SRP (5.6%) and EJ (4.2%). The presence of Ro52 associated with other MSA was found in 20 patients (22.9%).ILD was the most frequent manifestation (45.2% of the MSA+ve). Non-specific interstitial pneumonia (NSIP) was the most frequent ILD (39.5%), followed by usual interstitial pneumonia (34.2%). The main risk factors associated with IIM-ILD were some subtypes of the MSAs (pCancer was found in 9.6% of MSA+ve patients. The most frequent tumors were gynecological (37.5%), followed by gastrointestinal (25%) and breast cancer (12.5%). Factors associated with cancer were age (p=0.010), TIF1-γ (pThe mortality of these patients was 3.5%. There were no differences regarding MSA+ve/-ve (p = 0.911). However, MDA-5 (p=0.033) and older age (p=0.001) were associated with higher mortality. There were no significant differences between the IIM classifications, the associated SAD, the presence of cancer or ILD. However, longer follow-up periods and future studies are necessary to confirm these results.Conclusion:The use of a myositis blot allowed classifying, stratifying the risk of ILD, the risk of cancer and the risk of mortality in IIM. IIM-ILD was the most frequent complication, usually manifested as NSIP. The associated risk factors were ARS, OM, some MSAs, Ro52+ and older age. Cancer was a serious and frequent manifestation in these patients, especially in patients with TIF1-γ and other MSAs, so it is essential to know the risk factors and perform an early screening, especially in older patients.A better knowledge of the serological profiles of IIM will provide more individualized approaches and better risk stratification, helping in the management and treatment of these patients.References:[1]Satoh et al. Clin Rev Allergy Immunol. 2017 Feb;52(1):1-19.[2]Betteridge et al. J Intern Med. 2016 Jul;280(1):8-23.Disclosure of Interests:None declared

Background:Idiopathic inflammatory myopathies are a group of rare heterogeneous diseases that require a multidisciplinary and standardized approach.Objectives:To clinically characterize patients with inflammatory myopathies followed at an hospital’s Rheumatology Department, using the Rheumatic Diseases Portuguese Register (Reuma.pt).Methods:An observational transversal study was performed. Data on demographic variables, clinical features, antibodies and treatment were collected.Results:Of the 121 included patients, 78% were female, with a median age of 56 [44-68] years and a median disease duration of 2 [0-4] years. The most frequent diagnosis was dermatomyositis (DM; n=28, 23%) followed by antisynthetase syndrome (ASyS; n=21, 17.4%). At the time of the analysis, the median Manual Muscle Test (MMT-8) was 80 [78-80], the median modified skin Disease Activity Score was 0 [0-2] and global disease activity was 0.5 [0-0.75]. Calcinosis was found in 6% of the patients (n=7), mostly DM cases. Interstitial lung disease (ILD) was present in 29 patients (24%), of those, 52% (n=15) had antisynthetase syndrome (ASyS). Three patients presented as a paraneoplastic syndrome. Ninety-nine patients (82%) had a myositis autoantibody identified: antisynthetase autoantibodies were the most commonly identified (n=20, 16%). 62% of the patients were treated with steroids and 35% with ≥2 disease-modifying anti-rheumatic drugs.Table 1 depicts the main clinical characteristics and the immunologic profile for each diagnosisConclusion:In our cohort the most frequent myositis subtype was DM. Almost a quarter of patients had associated ILD, which is an important cause of morbidity and mortality. ILD was more frequent in ASyS patients and was most commonly related to anti-Jo1 antibodies, which is consistent with the literature.Table 1.Clinical characteristics and immunological profile of the patients.Diagnosis (n)Clinical featuresMyositis antibodies (n)Skin disease, median [IQR]/ (n)MMT-8, median [IQR]Lung disease (n)Others (n)Malignancy (n)Definite DM (28)DAS Skin 2 [0-2]Calcinosis (3)Mechanic hands (2)80 [75-80]NSIP (2);COP (1)Arthritis (6)Breast cancer (1)anti-Ro52 (6); anti-Mi2b (5); anti-PmScl100 (4); anti-MI2a (3); anti-NXP2 (3); anti-SAE (2); anti-MDA5 (2); anti-Ku (2); anti-Tif1g (1)Antisynthetase syndrome (21)DAS Skin 0 [0-0]Calcinosis (1)Mechanic hands (4)80 [80-80]NSIP (11);UIP (3);LIP (1)Arthritis (15);RP (10)–anti-Jo1 (14); anti-Ro52 (12); anti-Mi2b (1); anti-PL7 (3); anti-PL12 (1)Probable DM (19)DAS Skin 0 [0-0]80 [78-80]COP (1)Arthritis (5);RP (6)–anti-Mi2a (4); anti-Mi2b (2); anti-Tif1g (2); anti-Ku (2); anti-PmScl75 (2)CADM (16)DAS Skin 1 [0-2]Calcinosis (1)Mechanic hands (1)80 [77-80]NSIP (1); COP (1)Arthritis (5);RP (4)–anti-Mi2b (5); anti-Ro52 (2); anti-Mi2a (1); anti-MDA5 (1); anti-EJ (1); anti-SAE (1); anti-SRP (1); anti-Ku (1); anti-Tif1g (1)MCTD (12)DAS Skin 0 [0-1]80 [79-80]NSIP (1)Arthritis (8);RP (10)–anti-U1 RNP (12); anti-Ro52 (7)PM (7)DAS Skin 0 [0-0]Calcinosis (1)80 [72-80]NSIP (1)Arthritis (1)Ovarian cancer (1); non-Hodgkin lymphoma (1)anti-Ro52 (2); anti-SRP (1)UCTD (5)DAS Skin 0 [0-2]Calcinosis (1)Mechanic hands (1)80 [79-80]NSIP (2)Arthritis (1);RP (5)–anti-ThTo (2); anti-SRP (1); anti-PL12 (1)Overlap syndromes (12)DAS Skin 0 [0-2]Mechanic hands (2)80 [77-80]NSIP (3);UIP (1)Arthritis (4);RP (8)–anti-PmScl75 (4); anti-PmScl100 (1); anti-Ro52 (1); anti-Ro60 (1); anti-RNAPIII (1); anti-NOR90 (1); anti-MDA5 (1); anti-Ku (1)Necrotizing myopathy (1)DAS Skin 080––––DM – dermatomyositis; CADM – clinically amyopathic dermatomyositis; MCTD – mixed connective tissue disease; PM – polymyositis; UCTD – undifferentiated connective tissue disease; ILD – interstitial lung disease; NSIP – nonspecific interstitial pneumonia; LIP – lymphocytic interstitial pneumonitis; UIP – usual interstitial pneumonia; COP – cryptogenic organizing pneumonia; RP – Raynaud phenomenonDisclosure of Interests:None declared.

Background:Several reports have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may trigger a vigorous immune response that could lead to the appearance of various autoantibodies such as antinuclear antibodies, antiphospholipid antibodies or anti-neutrophil cytoplasmic antibodies, among others. Moreover, the pulmonary involvement in SARS-CoV-2 may resemble that of patients with anti-MDA5 positive syndrome or acute form of antisynthetase syndrome.Objectives:Our aim was to analyse the presence of anti-MDA5 and other myositis-specific autoantibodies such as the antisynthetase antibodies in patients diagnosed with severe acute respiratory syndrome caused by SARS-CoV-2.Methods:Retrospective observational study performed in a tertiary care center. We included 28 patients admitted to the intensive care unit with severe acute respiratory syndrome, 14 at the onset of the disease (group A) and 14 after 30 days of being treated in an intensive care unit (group B). Chest CT was performed at the admission. We analyzed the presence of anti-MDA5 and antisynthetase antibodies by immunoblot (Euroimmune®) and in those who were positive we performed a confirmatory test by immunoprecipitation.Results:All chest CT showed bilateral ground glass pattern. Three out of 14 patients of group A (12 males, 86%, mean ± SD age 67.1 ± 12.2) were positive for antisynthetase antibodies (2 anti-PL7, 1 anti-Jo1), and 6 out of 14 patients of the group B (6 males, 48%, mean ± SD age 68.7 ± 8.1) were positive to antisynthetase antibodies (2 anti-PL7, 2 anti-PL-12, 1 anti-EJ, 1 anti-OJ+PL7). Immunoblots also show positivity for other myositis-specific or associated antibodies, such as anti-TIF1g, anti-PM75, anti-SAE and anti-SRP. All of these results found by immunoblotting were negative by immunoprecipitation. None of the 28 patients were positive for anti-MDA5 antibodies.Conclusion:Severe SARS-CoV-2 pneumonia is characterized by ground glass pattern in chest CT, as it is found in anti-MDA5 or antisynthetase syndrome. The positivity of several myositis related autoantibodies showed in immunoblot appears to be more related to the vigorous immune response producing polyclonal immunoglobulins than triggering a real myositis-associated interstitial lung disease. Clinicians must be aware about these false positive results in patients with severe COVID-19 acute respiratory syndrome.References:[1]Xu Q. MDA5 should be detected in severe COVID-19 patients. Med Hypotheses. 2020; 143:109890.[2]Giannini M, Ohana M, Nespola B, Zanframundo G, Geny B, Meyer A. Similarities between COVID-19 and anti-MDA5 syndrome: what can we learn for better care? Eur Respir J. 2020; 56:2001618.[3]Vlachoyiannopoulos PG, Magira E, Alexopoulos H, Jahaj E, Theophilopoulou K, Kotanidou A, Tzioufas AG. Autoantibodies related to systemic autoimmune rheumatic diseases in severely ill patients with COVID-19. Ann Rheum Dis. 2020 Dec;79(12):1661-1663Disclosure of Interests:None declared

Background:The antisynthetase syndrome (SAS) is characterized by the presence of antisynthetase antibodies, anti-JO1, PL7 y PL12 are the most common; and the classic triad of myositis, arthritis, and diffuse interstitial lung disease (ILD)1. Most patients present incomplete forms and the severity of the ILD determines the prognosis of the disease2.Objectives:to analyze epidemiological, clinical and serological characteristics and treatments used in a cohort of patients with SAS.Methods:descriptive study of review of medical records. Data were collected from 15 patients with SAS followed in the Rheumatology and Pneumology consultations of the Virgen Macarena Hospital (Seville) in the last 10 years. The analysis was carried out using the R software.Results:15 patients were included, 8 men and 7 women. The median age was 56 years (33-77). Seven patients (47%) used to smoke. Four patients (27%) met the classical triad. All of them presented ILD and 8 patients (53%) had arthritis and / or myositis. Five (33%) had mechanic’s hands and six of them (40%) presented Raynaud. Seven (47%) suffered from dyspnea before the SAS diagnosis. The median diagnostic delay was 1 month (0-43). Seven (47%) patients had anti-JO1, 1 (7%) anti-PL7, 2 (13%) anti-PL12 and 2 (13%) patients anti-Ro52. Radiological patterns detected by HRCT were: 5 (33%) NINE, 4 (37%) NIU and 6 (40%) others. The initial treatment included mostly (66%) glucocorticoids (GC) and one or more cFAME. In maintenance, mycophenolate was used in 7 patients (47%), cyclosporine 5 (33%), cyclophosphamide in 3 cases (20%), azathioprine in 3 patients (20%) and methotrexate in 3 of them (20%). Four (37%) patients required a combination of DMARDs and 2 cases needed (13%) biological therapy, Rituximab and Tocilizumab. Changes in the mean value of the initial respiratory function tests (FVC1 and DLCO1) and during follow-up (FVC2 and DLCO2) were not relevant (FVC1 81.5% [42-110], FVC2 81% [59-115]; DLCO1 83% [10-112], DLCO2 80.5% [47-108]). Nine patients (60%) remained clinically stable and 3 patients (20%) progressed radiologically. Four patients died from ILD progression.Conclusion:In this study, the incomplete diagnosis of SAS predominated. The most detected antibody was anti-JO1. ILD is present in all cases, with NINE being the most frequent pattern so multidisciplinary management is necessary. Most used treatments were GC and FAMES combined, some cases required biological therapy.References:[1]Irazoque F, et al. Epidemiology, etiology and classification. Reumatol Clin. 2009;5:2-5.[2]Johnson C, et al. Clinical and pathologic differences in interstitial lung disease based on antisynthetase antibody type. Respir Med. 2014; 108(10):1542-8.Disclosure of Interests:None declared

Background:Idiopathic inflammatory myopathies (IIM) are autoimmune diseases that mainly affect skeletal muscle, lung, skin and joints. IIM can be separated into dermatomyositis (DM), inclusion body myositis (IBM), antisynthetase syndrome (AS) and immune-mediated necrotizing myopathy (IMNM). Type I interferons (IFN) are known to play a crucial role in the etiopathogenesis of some of these entities such as DM.[1] Sialic acid binding Ig-like lectin 1 (SIGLEC1, CD169) is part of the type I IFN signature found in SLE and DM and is expressed on the cell surface of monocytes. Thus, analysis of SIGLEC1 expression by flow cytometry enables a straightforward assessment of the type I IFN signature. Its utility has been shown for juvenile and adult SLE and other rheumatic diseases but not in IIM.[2,3] The assessment of the type I IFN system in clinical practice is an unmet need and, in this context, SIGLEC1 might be useful.Objectives:To assess SIGLEC1 expression on monocytes by flow cytometry as a type I IFN biomarker in IIMMethods:Pediatric and adult patients with a clinical diagnosis of DM, AS, IMNM and IBM and at least one measurement of SIGLEC1 who have been treated at the Department of Rheumatology, Charité - Universitätsmedizin Berlin between 2015 and 2020 were included in this retrospective study. Control groups of healthy individuals (n=19) and SLE patients (n=30) were included. Disease activity was assessed by Physician Global Assessment (PGA) and Childhood Myositis Assessment Scale (CMAS). SIGLEC1 expression on monocytes was analyzed by flow cytometry. Cross-sectional analyses (n=74) were performed using Mann Whitney-U test (MWU) and two-level mixed-effects linear regression model was used for longitudinal analyses (n=26, 110 visits). This study was approved by the local ethics committee of the Charité - Universitätsmedizin Berlin.Results:74 patients (adult/juvenile DM: n=21/n=17; AS: n=19; IMNM: n=8; IBM: n=9) were included. In cross-sectional analysis, SIGLEC1 expression was significantly upregulated in adult and juvenile DM patients with moderate to severe disease activity (PGA≥5) compared with adult/juvenile DM patients with no to moderate disease activity (PGAConclusion:SIGLEC1 is a useful biomarker to identify an activated type I IFN system in IIM. Flow cytometry is used widely in laboratory medicine, which could facilitate the implementation of SIGLEC1 into clinical routine.References:[1]Gallay L, Mouchiroud G, Chazaud B. Interferon-signature in idiopathic inflammatory myopathies: Current Opinion in Rheumatology 2019;31:634–42. doi:10.1097/BOR.0000000000000653[2]Rose T, Grutzkau A, Hirseland H, et al. IFNalpha and its response proteins, IP-10 and SIGLEC-1, are biomarkers of disease activity in systemic lupus erythematosus. Ann Rheum Dis 2013;72:1639–45. doi:10.1136/annrheumdis-2012-201586[3]Stuckrad SL von, Klotsche J, Biesen R, et al. SIGLEC1 (CD169) is a sensitive biomarker for the deterioration of the clinical course in childhood systemic lupus erythematosus. Lupus 2020;:961203320965699. doi:10.1177/0961203320965699Figure 1.SIGLEC1 expression on monocytes in IIM subgroups and control groups; in IIM subgroups, patients with low disease activity (PGADisclosure of Interests:None declared

Background:Antisynthetase syndrome (ASyS) may have different clinical phenotypes and outcomes associated with different anti-aminoacyl RNA-synthetase (anti-ARS) antibodies. Its wide clinical spectrum can include inflammatory myopathy, interstitial lung disease (ILD), arthritis, fever, mechanic’s hands, and Raynaud phenomenon (RP).Objectives:To describe a nationwide, multicentre cohort of Portuguese patients with ASyS.Methods:Retrospective analysis of patients with ASyS from nine Portuguese Rheumatology centers. Data on patients’ signs and symptoms, laboratory results, pulmonary radiological findings (computed tomography) and treatment (immunomodulators) were collected.Results:Among the 70 patients included, 42 patients (60%) were anti-Jo1–positive, 11 (15.7%) were anti-PL12–positive, 10 (14.3%) were anti-PL7–positive, 4 (5.7%) were anti-EJ–positive and 2 (2.9%) were anti-OJ positive. In one patient it was not possible to identify the type of antibody. Antibody overlap was found in 15 patients (21.4%), who were positive for anti-Ro52 antibodies. The general clinical characteristics are shown in Table 1. The diagnostic delay was greater in patients positive for anti-OJ, followed by anti-Jo-1 and anti-PL12. The follow-up was shorter for anti-PL7 and anti-OJ-positive patients. Anti-PL7-positive patients had lower rates of arthritis when compared to anti-Jo1 (p< 0.01). When compared with anti-Jo-1 ARS, myositis was less common in anti-PL12 (p < 0.01). ILD prevalence was similar in the different ARS subgroups. Glucocorticoids (GCs) were the most frequently used class of drugs. A more conservative treatment plan (e.g. GCs plus methotrexate or azathioprine) was the treatment of choice in ASyS with myositis and/or arthritis involvement. Rituximab or mycophenolate mofetil were preferred when lung involvement occurred. Only two deaths were reported, being one associated with lung neoplasia.Conclusion:This is the first study investigating the clinical phenotypes of Portuguese patients with ASyS. These results are generally concordant with data retrieved from international cohorts.References:[1]Mahler M, Miller FW, Fritzler MJ. Idiopathic inflammatory myopathies and the anti-synthetase syndrome: a comprehensive review. Autoimmun Rev 2014;13:367–71.Table 1.Patient characteristics according to the anti-ARS. ILD - interstitial lung disease; IQR- interquartile range; NSIP - Non-specific interstitial pneumonia; UIP - Usual interstitial pneumonia; yrs - yearsVariablesOverall, n=70Jo-1, n=42(60%)PL-12, n=11 (15.7%)PL-7, n=10 (14.3%)EJ, n=4 (5.7%)OJ, n=2 (2.9%)Mean age at onset, yrs52 ± 1546.6 ± 14.455.2 ± 14.756.5±12.556.3±11.273.5±2.1Female, n (%)49 (70)29 (69)9 (81.8)7 (70)2 (50)2 (100)Median age in years at disease onset (IQR)52 (15-75)48 (15-70)59 (20-70)62 (39-73)60 (40-65)73.5 (72-75)Median follow-up time in yrs (IQR)3 (0-32)5 (0-32)3 (0-13)1 (1-4)4 (2-21)1 (0-2)Median diagnostic delay in yrs (IQR)6 (1-33)7 (1-33)7 (2-19)4 (1-23)1.5 (1-2)12.5 (2-21)Myositis, n (%) and Comparison Anti-Jo.1 ARS vs PL-12 and PL-736 (51.4)25 (59.5)3 (27.3)*p < 0.014 (40)p=0.73 (75)-0-ILD, n (%) and Comparison Anti-Jo.1 ARS vs PL-12 and PL-753 (75.7)33 (78.6)8 (72.7)p = 0.986 (60) p=0.564 (100)-1 (50)- ILD pattern - NSIP, n (%)30 (56.6)18 (54.5)6 (75)3 (50)1 (25)0 ILD pattern - UIP, n (%)6 (11.3)3 (9.1)1 (12.5)1 (16.7)1 (25)0 ILD pattern - other specific pattern, n (%)6 (11.3)4 (12.1)02 (33.3)1 (25)0 ILD pattern - non-specific pattern, n (%)11 (15.7)8 (24.2)1 (12.5)01 (25)1 (100)Mechanic’s hands (%), n (%)23 (32.9)14 (33.3)3 (27.3)2 (20)01 (50)General impairment, n (%)18 (25.7)11 (26.2)3 (27.3)2 (20)2 (50)0Fever, n (%)7 (10)4 (9.5)2 (20.2)01 (25)0Raynaud phenomenon, n (%)22 (31.4)11 (26.2)7 (63.6)02 (50)0Arthritis, n (%) and Comparison Anti-Jo.1 ARS vs PL-12 and PL-743 (61.4)29 (69)5 (45.4)p=0.072 (20)*p < 0.012 (50)-1 (50)-Malignancy, n (%)4 (5.7)3 (7.1)1 (9.1)000Deaths, n (%)2 (2.9)2 (2.4)0001 (50)Disclosure of Interests:None declared

Background:Antisynthetase syndrome (ASS) is characterized by inflammatory myopathy, interstitial lung disease, arthritis, mechanical hands and Raynaud phenomenon, among other features. Recent studies have shown that idiopathic inflammatory myopathies (IIM) may develop cardiac involvement, either ischemic (coronary artery disease) or inflammatory (myocarditis). We wonder if characteristic lung interstitial involvement (interstitial lung disease) that appears in patients with the ASS may also affect the myocardial interstitial tissue. New magnetic resonance mapping techniques could detect subclinical myocardial involvement, mainly as edema (increase extracellular volume in interstitium and extracellular matrix), even in the absence of visible late Gadolinium enhancement (LGE).Objectives:Our aim was to describe the presence of interstitial myocarditis in a group of patients with ASS.Methods:Cross-sectional, observational study performed in a tertiary care center. We included 13 patients diagnosed with ASS (7 male, 53%, mean (SD) age at diagnosis 56,8 years (±11,8)). The patients were consecutively selected from our outpatient myositis clinic. Myositis specific and associated antibodies were performed by means of line immunoblot (EUROIMMUN©). Cardiac magnetic resonance (CMR) was performed on all patients. The study protocol includes functional cine magnetic resonance and standard late gadolinium enhancement (LGE), as well as novel parametric T1 and T2 mapping sequences (modified look locker inversion recovery sequences - MOLLI) with extracellular volume (ECV) calculation 20 minutes after the injection of a gadolinium-based contrast material.Results:CMR could not be performed in one patient due to anxiety. All patients studied (12) had a normal biventricular function, without alteration of segmental contraction. A third (4 out of 12, 33%) of the studied patients showed elevated T2 myocardial values without focal LGE, half of them (2/4) with an elevated ECV, consistent with myocardial edema. Two patients with normal T2 values showed unspecific LGE focal patterns, one in the right ventricle union points and another with mild interventricular septum enhancement (Figure 1). None of the patients studied refer any cardiac symptomatology. All the four patients with T2 mapping alterations (100%) had interstitial lung involvement, but only 4 out of 8 (50%) of the rest ASS patients without T2 mapping positivity. The autoimmune profile was as follows: 10 anti-Jo1/Ro52, 1 anti-EJ/Ro52, 2 anti-PL12.Conclusion:Myocarditis, although subclinical, appears to be a feature in ASS patients. T1 and T2 mapping sequences might be valuable to detect and monitor subclinical cardiac involvement in these patients. The possibility that the same etiopathogenic mechanism may be involved in the interstitial tissue in lung and myocardium is raised. More studies must be done in order to assert the prevalence of myocarditis in ASS.References:[1]Dieval C et al. Myocarditis in Patients With Antisynthetase Syndrome: Prevalence, Presentation, and Outcomes. Medicine (Baltimore). 2015 Jul;94(26):e798.[2]Myhr KA, Pecini R. Management of Myocarditis in Myositis: Diagnosis and Treatment. Curr Rheumatol Rep. 2020 Jul 22; 22:49.[3]Sharma K, Orbai AM, Desai D, Cingolani OH, Halushka MK, Christopher-Stine L, Mammen AL, Wu KC, Zakaria S. Brief report: antisynthetase syndrome-associated myocarditis. J Card Fail. 2014 Dec;20(12):939-45.Figure 1.Cardiac magnetic resonance images from ASS patients.Disclosure of Interests:None declared

We report a complex case of a 66-year-old female patient with a diagnosis of interstitial lung disease (ILD) that was later correctly identified as an antisynthetase syndrome. This was only diagnosed after an episode of sustained ventricular tachycardia secondary to myocarditis. In this case report, we focus on the clinical features of this rare autoimmune condition and aim to provide useful tips to both general medical professionals and cardiologists to achieve correct differential diagnosis according to the updated international guidelines and recommendations. Early diagnosis is especially important due to the possible arrhythmogenic complications and the high mortality and morbidity associated with ILD and cardiac abnormalities.

Background:Inflammatory myopathies (IM) are a group of rare diseases that involve muscle inflammation. Several types are defined with a wide range of different manifestations and prognosis.Objectives:Describe the characteristics of the cohort of patients with IM in a tertiary hospital, in order to identify their demographic and clinical characteristics and try to find a correlation between them.Methods:Retrospective observational study of patients with IM: dermatomyositis (DM), polymyositis, antisynthetase syndrome (ASS), necrotizing autoimmune myopathy and overlap syndrome (OS). Clinical, biological, neurophysio and histopathological data were collected. Statistical analysis was performed using SPSS 23 IBM®.Results:28 patients were included with a follow-up of 10.9 ± 9.8 years (y). According to the 2017 EULAR / ACR criteria for IM, 89.2% were classified as definitive MI, with an average score of 12.1 ± 3.2. Age at diagnosis 47.3 ± 17.7y; ratio 1.3; 78.6% Caucasian, 10.7% Asian and 10.7% Latino. 39.3% had DM, 3.6% hypomyopathic and 3.6% amyopathic DM, 28.6% OS and 17.9% ASS. Lung involvement was the most prevalent extramuscular manifestation (67.9%). Systemic sclerosis was the most frequent overlapping autoimmune disease (AD) (21.4%) and 2 patients (7.1%) overlapped more than 1 AD. In Table 1 are detailed the clinical characteristics of the patients, and in Figures 1 and 2, the autoantibody (aa) profile and treatments used. The incidence of neoplasm was 10.7% 10.3 ± 9.6y after the diagnosis of myopathy (3 breast neoplasms, 1 colon and 1 cutaneous lymphoma), and of them, 66.7% had two synchronous neoplasms. No neoplasms were observed in the 2 anti-TIF1-γ+ patients. The subtype of IM in these patients was 1 OS anti-RNP+, 1 DM anti-PL-12+ and 1 ASS anti-OJ+. 17.9% smoked and 21.4% had taken statins at some point, without it being related to the start of the myopathic clinic. A capillaroscopy was performed in 67.9%, being pathological in 63.1%The positivity of anti-RNP (p=0.01) and steroid bolus (p=0.039) were correlated with a more severe disease, defined as a summation index composed of a series of manifestations (pulmonary hypertension (PH), ischemic heart disease, venous/arterial thrombosis, myo/pericarditis, interstitial lung disease (ILD), severe infections, neoplasms or hospitalizations). Other statistically significant correlations between aa and clinical manifestations are detailed in Table 3, among which the anti-RNP+ with myopericarditis stands out. No correlation was found between the findings on capillaroscopy and the type of IM.Conclusion:The most frequent subtype of IM was DM. 10.3% of the patients presented a neoplasm, all with different subtypes of myopathy and aa. The presence of anti-RNP+ correlated with greater severity of the disease and myopericarditis. Likewise, significant differences were found between the subtypes of aa and certain clinical manifestations. There is no correlation between findings on capillaroscopy and the type of IM.Table 1.Clinical characteristics.Clinical manifestationsFrequency %PresentationAcute40.7Subacute22.2Insidious37Muscular Weakness82.1Muscle Enzymes Elevation85.7Muscle Pain67.9Joint Manifestations (Mf)67.9Systemic Mf67.9Digestive Mf46.4Raynaud’s Syndrome (RS)53.6Sclerodactyly32Digital ulcers (DU)25Calcinosis10.7ILD67.9Nonspecific Interstitial Pneumonia63.2Usual Interstitial Pneumonia15.8Organizing Pneumonia10.5Lymphocytic Interstitial Pneumonia5.3Undefined Pattern5.3PH10.7Serious Infections17.9Figure 1.Aa.Figure 2.Treatment.Table 2.Correlations between clinical manifestations and aa.ManifestationsAutoantibodiesp valueDUAnti-MDA50.005SclerodactylyAnti-RNP0.011PericarditisAnti-RNP0.000MyocarditisAnti-RNP0.005DiabetesAnti-RNP0.027RSAnti-PM/Scl0.033CalcinosisAnti-PM/Scl0.027Flexion ContracturesAnti-PM/Scl0.027ArrhythmiasAnti-PL-120.001Disclosure of Interests:Irene Carrión Barberà Grant/research support from: I received a grant from the Spanish Rheumatology Foundation (FER) and laboratories KERN PHARMA for a brief stay abroad., Ana Pros Simón: None declared, Tarek Carlos Salman Monte: None declared, Manel Ciria: None declared, Francisco Vílchez-Oya: None declared, Selene Labrada: None declared, Toni Meraz: None declared, Jordi Monfort: None declared

Background:In SSc, skin involvement of the face is frequent and extremely disabling, resulting in limited mouth opening, an altered dentition, difficulty in teeth care, as well as having a strong impact on the emotional and psychological well-being, thus impairing quality of life.Objectives:to evaluate the efficacy of a self-treatment protocol (created by AMURR A Multidisciplinary Association of Rheumatological Rehabilitation) for face and tempomandibular joints (TMJs) rehabilitation with two devices used in the dental field.Methods:40 SSc patients (37 female and 3 male) with a mouth opening ≤ 40 mm, were recruited and randomized in two groups of treatment: Group 1 (20 patients: mean age 50,650 yrs ± 13,937 SD, mean disease duraton 10,45 yrs ± 7,877 SD, opening mouth 32,250 mm ± 5,590 SD) treated with a home self-treatment protocol consisting of 23 exercises carried out at home in front of a mirror, 22/23 exercises were performed once a day, one of these using a device to obtain uniform stretching of the buccal rhyme, another one usingused three times a day to reduce tension of muscles of the TMJs, facilitating the mouth opening; group 2 (20 patients: mean age 58,05 yrs ± 18,103 SD, mean disease duration 17,4 yrs ± 15,017 SD, opening mouth 34,950 mm ± 5,753) without physical rehabilitation, only drugs as treatments of SSc and its complications. All patients underwent a baseline (T0) and 45 days (T1) clinimetric assessment by self-assessment of quality of life with SF-36 (Short-Form 36 Health Survey), of the degree of disability of the mouth with MHISS (of the Mouth Handicap in Systemic Sclerosis scale), Muscle pain evaluated by numerical rating scale (NRS) of the temporomandibular joint with TMD (Temporo mandibular Disorders), evaluation of mouth opening and ROM of the cervical spine. Statistical analysis was performed using the t-test or the Mann-Whitney test for assessing changes in all measurement scales between treatment groups.Results:The protocol of home physiotherapy exercises resulted in a statistically significant improvement in the treated group compared to group 2 both for mouth opening (T0: 32,250 ± 5,590, T1: 35,650 ± 6,046) vs (T0: 34,950 ± 5,753 T1: 34,300 ± 6,001) (pConclusion:The use of the home exercises protocol associated with the two devices has shown a significant improvement of the disability linked to skin involvement of the face. This highlights the fundamental role that home rehabilitation self therapy has in practice. These data will need to be confirmed in a larger cohort of patientsDisclosure of Interests:Mauro Passalacqua: None declared, Cristian Foggi: None declared, Nicola Mauro: None declared, Lorenzo Tofani: None declared, Serena Guiducci: None declared, Cosimo Bruni Speakers bureau: Actelion, Eli Lilly, Gemma Lepri: None declared, Jelena Blagojevic: None declared, Khadija El Aoufy: None declared, Ginevra Fiori: None declared, Francesca Bartoli: None declared, Susanna Maddali Bongi: None declared, Marco Mitola: None declared, Marco Gizduloch: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Bristol-Myers Squibb, Speakers bureau: Acetelion, Lilly, Boehringer Ingelheim, Silvia Bellando Randone: None declared

Background:Idiopathic inflammatory myopathies (IIM) are a group of immune-mediated diseases characterized my muscle weakness, skin rash and systemic involvement. Myositis-specific antibodies (MSA) and myositis-associated antibodies (MAA) play a major role in IIM diagnosis, classification and prognosis. Nevertheless, MSA/MAA testing is not standardized and there very few studies addressing their relationship with other diseases.Objectives:To describe a cohort of patients tested positive for MSA/MAA, and to explore it´s relationship with IIM and other autoimmune diseases.Methods:We retrospectively review all the serum samples obtained from patients tested for MSA/MAA during 2019 in the Immunology department of Ramón y Cajal University Hospital (Madrid, Spain). These antibodies were tested by specific immunoblot (EUROLINE: Autoimmune Inflammatory Myopathies 16 Ag) with highly purified MSA/MAA. Positivity was stablished according to absorbance titer and adjusted by positive control of each test (arbitrary units, AU). Patients were diagnosed with IIM according to their clinician diagnosis. Diagnosis and classification were confirmed by an independent rheumatologist (JL) according to current understanding of IIM classification.Results:Three-hundred-seventy-five samples were tested for MSA during the study period. Two-hundred-seventy-nine were negative for all antibodies tested. Ninety-six samples were positive for one or more MSA/MAA, corresponding to 74 patients (11 patients had 2 different samples). Forty-nine (66.2%) of the patients who tested positive were female and 25 (33.8%) were male. Mean age was 58.65 years. Only 22 patients (29.7%) had a confirmed diagnosis of IIM, 24 (32.4%) had a diagnosis of other autoimmune disease, and 11 (14.9%) were diagnosed with interstitial lung disease (ILD) (Figure 1). Six ILD patients had anti-PM-Scl or anti-Ku antibodies, which are associated with scleroderma or overlap-CTD myositis, nevertheless, they remained classified as ILD as no other features were described in this group.Seventeen patients were positive for more than 1 MAA or MSA, including 14 patients positive for anti Ro-52. Antibody titer was higher in the IIM group compared to non-myositis group (59.59 vs 44.16, p=0.015). Anti Mi-2 was positive in 4 ILD without any other myositis features, and high titer anti-SRP (n=4, mean 59.75 AU) was found in primary biliary cirrhosis (PBC) patients. Additionally, 5 patients positive for antiJo-1 using ELIA (Thermo Fisher) were diagnosed with antisynthetase syndrome. IIM diagnosis and its relationship with antibody titer is represented in table 1.Table 1.Autoantibody titer according to diagnosis.Antibody (Number of patients)Number of samplesIIMIIM antibody titer (AU)Non-IIMNon-IIM antibody titer (AU)Other AI diseasesAnti Ro-52Anti Jo-1 (n=1)11 (100%)92.70-01 (100%)Anti PL-7 (n=8)113 (37.5%)29.595 (62.5%)25.595 (62.5%)2 (25%)Anti PL-12 (n=3)21 (33.3%)53.952 (66.6%)69.971 (33.3%)2 (50%)Anti EJ (n=1)11 (100%)99.460-01 (100%)Anti OJ (n=2)40-2 (100%)23.041 (50%)0Anti Ku (n=14)193 (21.4%)107.2511 (78.6%)31.855 (35.7%)0Anti Tif1gamma (n=5)63 (60%)40.122 (40%)23.841 (20%)0Anti NXP2 (n=2)30-2 (100%)13.991 (50%)1 (50%)Anti Mi2 (n=12)173 (25%)48.659 (75%)26.674 (33.3%)0Anti SAE (n=1)10-1 (100%)1800Anti MDA5 (n=2)32 (100%)30.5401 (50%)1 (50%)Anti SRP (n=9)124 (44.4%)42.695 (55.6%)68.165 (55.5%)2 (22.2%)Anti PM-Scl75 and PM-Scl100 (n=2)21 (50%)68.61 (50%)36.6700Anti PM-Scl75 (n=8)10016.268 (100%)22.723 (37.5%)1 (12.5%)Anti PM-Scl100 (n=4)50-4 (100%)23.622 (50%)0Conclusion:Only 28.7% of the patients that were MAA/MSA positive had a diagnosis of IIM. Other autoimmune diseases and ILD were commonly found in this group of MSA/MAA positive patients.References:[1]Damoiseaux J, Vulsteke JB, Tseng CW, Platteel ACM, Piette Y, Shovman O, et al. Autoantibodies in idiopathic inflammatory myopathies: Clinical associations and laboratory evaluation by mono- and multispecific immunoassays. Vol. 18, Autoimmunity Reviews. Elsevier B.V.; 2019. p. 293–305.Disclosure of Interests:None declared

Background:Nailfold Videocapillaroscopy (NVC) is an essential tool for the assessment of Raynaud’s Phenomenon (RP) among the Scleroderma Spectrum Disorders (SSDs). Recently, NVC abnormalities have been associated with a diagnosis of Idiopathic Inflammatory Myopathies (IIMs), independently of the presence of RP (1). Moreover, both SSDs and IIMs are commonly associated with Interstitial Lung Disease (ILD), which is the main cause of mortality in these conditions.Objectives:To verify whether NVC may allow a better diagnostic classification in a cohort of patients with ILD followed by pulmonologists.Methods:361 patients affected by ILD were prospectively enrolled in a 30-months observational study. All these patients were clinically evaluated by rheumatologists and pulmonologists together and performed general blood tests, autoantibody research, chest High-Resolution Computed Tomography and NVC. The latter was considered positive in the presence of avascular areas or giant capillaries, and also the presence of Bushy Capillaries (BCs) was recorded.Results:NVC was positive in 17.7% of ILD patients, and a third of these patients did not present RP. Patients with NVC abnormalities had a diagnosis of definite Connective Tissue Disease in 78.1% of cases. NVC resulted decisive in 25% of patients with a final diagnosis of Systemic Sclerosis according to the ACR/EULAR 2013 criteria. The presence of BCs and/or NVC+ in ILD patients with normal serum levels of muscular enzymes was associated with amyopathic IIM (BCs= OR 3.9, 95CI 1.05-14.38, p=0.04; NVC+= OR 5, 95CI 1.29-19.3 p=0.02; BCs and/or NVC+= OR 5.41 95CI 1.24-23.48 p=0.02), regardless the presence of RP.Conclusion:NVC proved to be a valid tool in the correct assessment of ILD patients secondary to SSDs and amyopathic IIMs. Therefore, it could be considered in the diagnostic evaluation of patients affected by ILD, regardless of the presence of RP.References:[1]Sebastiani M et al. Nailfold Capillaroscopy Characteristics of Antisynthetase Syndrome and possible clinical associations: results of a multicenter International Study.J Rheumatol2019; 46: 279-284Table 1.Comparison between ILD patients with and without NVC positivity..ItemsNVC+ patientsNVC- patientspNumber64297Mean Age (±SD)61.4±13.367.8±9.80.001Female%65.649.10.01RP%68.717.1HRCT patterns%NSIP51.536.80.02OP3.18n.s.UIP-like31.1544.8n.s.DIP1.53.4n.s.LIP1.50.4n.s.Indeterminate10.96.7n.s.Final Diagnosis%SSDs45.31IIMs256.4Other CTDs6.213.5n.s.IPAF10.919.5n.s.IPF7.827.90.0007Legend:DIP: Desquamative Interstitial Pneumonia; HRCT: High Resolution Computed Tomography; IIMs: Idiopathic Inflammatory Myopathies, Poly/dermatomyositis, antisynthetase syndrome; IPAF: Interstitial Pneumonia with Autoimmune Features; IPF: Idiopathic Pulmonary Fibrosis; LIP: Lymphocytic Interstitial Pneumonia; NSIP: Nonspecific Interstitial Pneumonia; OP: Organising Pneumonia; RP: Raynaud’s Phenomenon; SSDs: Scleroderma Spectrum Disorders, Systemic Sclerosis + Mixed Connective Tissue Disease; UIP: Usual Interstitial Pneumonia.Disclosure of Interests:Gianluca Sambataro: None declared, Domenico Sambataro: None declared, Francesca Pignataro: None declared, Nicoletta Del Papa: None declared, Michele Colaci: None declared, Lorenzo Malatino: None declared, Alessandro Libra: None declared, Fabio Pino: None declared, Sebastiano Emanuele Torrisi Speakers bureau: Boehringer Ingelheim; F. Hoffmann-La Roche Ltd., Stefano Palmucci Consultant of: Boehringer Ingelheim, Speakers bureau: Boehringer Ingelheim, Delphi International Srl, and F. Hoffmann-La Roche Ltd., Lorenzo Cavagna: None declared, Carlo Vanchieri Grant/research support from: F. Hoffmann-La Roche Ltd., Consultant of: AstraZeneca, Boehringer Ingelheim, Chiesi, F. Hoffmann-La Roche Ltd., and Menarini, Speakers bureau: AstraZeneca, Boehringer Ingelheim, Chiesi, F. Hoffmann-La Roche Ltd., and Menarini

Background: Inflammatory myopathies (IM) are a group of rare diseases that involve muscle inflammation. Several types are defined with a wide range of different manifestations and prognosis. Objectives: Describe the characteristics of the cohort of patients with IM in a tertiary hospital, in order to identify their demographic and clinical characteristics and try to find a correlation between them. Methods: Retrospective observational study of patients with IM: dermatomyositis (DM), polymyositis, antisynthetase syndrome (ASS), necrotizing autoimmune myopathy and overlap syndrome (OS). Clinical, biological, neurophysio and histopathological data were collected. Statistical analysis was performed using SPSS 23 IBM®. Results: 28 patients were included with a follow-up of 10.9 ± 9.8 years (y). According to the 2017 EULAR / ACR criteria for IM, 89.2% were classified as definitive MI, with an average score of 12.1 ± 3.2. Age at diagnosis 47.3 ± 17.7y; ratio 1.3; 78.6% Caucasian, 10.7% Asian and 10.7% Latino. 39.3% had DM, 3.6% hypomyopathic and 3.6% amyopathic DM, 28.6% OS and 17.9% ASS. Lung involvement was the most prevalent extramuscular manifestation (67.9%). Systemic sclerosis was the most frequent overlapping autoimmune disease (AD) (21.4%) and 2 patients (7.1%) overlapped more than 1 AD. In Table 1 are detailed the clinical characteristics of the patients, and in Figures 1 and 2, the autoantibody (aa) profile and treatments used. The incidence of neoplasm was 10.7% 10.3 ± 9.6y after the diagnosis of myopathy (3 breast neoplasms, 1 colon and 1 cutaneous lymphoma), and of them, 66.7% had two synchronous neoplasms. No neoplasms were observed in the 2 anti-TIF1-γ+ patients. The subtype of IM in these patients was 1 OS anti-RNP+, 1 DM anti-PL-12+ and 1 ASS anti-OJ+. 17.9% smoked and 21.4% had taken statins at some point, without it being related to the start of the myopathic clinic. A capillaroscopy was performed in 67.9%, being pathological in 63.1% The positivity of anti-RNP (p=0.01) and steroid bolus (p=0.039) were correlated with a more severe disease, defined as a summation index composed of a series of manifestations (pulmonary hypertension (PH), ischemic heart disease, venous/arterial thrombosis, myo/pericarditis, interstitial lung disease (ILD), severe infections, neoplasms or hospitalizations). Other statistically significant correlations between aa and clinical manifestations are detailed in Table 3, among which the anti-RNP+ with myopericarditis stands out. No correlation was found between the findings on capillaroscopy and the type of IM. Conclusion: The most frequent subtype of IM was DM. 10.3% of the patients presented a neoplasm, all with different subtypes of myopathy and aa. The presence of anti-RNP+ correlated with greater severity of the disease and myopericarditis. Likewise, significant differences were found between the subtypes of aa and certain clinical manifestations. There is no correlation between findings on capillaroscopy and the type of IM. Disclosure of Interests: Irene Carrion Barbera Grant/research support from: I received a grant from the Spanish Rheumatology Foundation (FER) and laboratories KERN PHARMA for a brief stay abroad., Ana Pros Simon: None declared, Tarek Carlos Salman Monte: None declared, Manel Ciria: None declared, Francisco Vilchez-Oya: None declared, Selene Labrada: None declared, Toni Meraz: None declared, Jordi Monfort: None declared

Background:Antisynthetase syndrome is an autoimmune rheumatologic disease characterized by the presence of specific antibodies that are known as antisynthetase antibodies and with a varied clinic, including arthritis, myositis or interstitial lung disease (ILD), among others. ILD is the manifestation that associates the highest morbi / mortality and can occur with different characteristic radiological patterns: usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP), organized pneumonia (OP)Objectives:Describe the clinical, serological and prognostic characteristics of patients with antisynthetase syndrome with interstitial pulmonary involvement (ILD) based on their radiological pattern.Methods:Retrospective descriptive study of patients with a clinical diagnosis of antisynthetase syndrome in which they show positive for some antisynthetase antibody and with clinical follow-up of at least 6 months in a reference center consultation between the period from January 2008 to September 2019. In those patients who presented interstitial lung involvement clinical, analytical and prognostic variables were evaluated (including spirometry) based on the radiological pattern presented by high-resolution computed tomography (HRCT) of the chestResults:32 patients (24 women and 8 men) were included in the study. 7 cases (21.9%) did not present pulmonary involvement, while the remaining 25 cases (78.1%) presented with interstitial lung involvement. Of the patients diagnosed with ILD, 4 cases (12.5%) had an interstitial pattern UIP, 17 cases (53.1%) had an interstitial pattern of NSIP and another 4 (12.5%) interstitial pattern of OP. From an analytical point of view, the most frequent antisynthetase antibody in our sample was antiJo1 with 29 cases (96.9%) and less frequently the antiPL12 antibody with 2 cases and antiPL7 with 1 case. The specific characteristics depending on the type of EPID pattern are summarized in Table 1.Table 1.CHARACTERISTICSILD PATTERNPattern UIP N=4Pattern NSIP N=17Pattern OP N=4Gender (Female) n (%)4 (100)11 (64.7)3 (75.0)Age at diagnosis47.5 ± 12.952.9 ± 10.542.0 ± 12.9Myositis, n(%)2 (50.0)13 (76.5)4 (100)Arthritis, n (%)3 (75.0)15 (88.2)3 (75.0)Fever, n (%)1 (25.0)9 (52.9)2 (50.0)Mechanic´s hands, n(%)2 (50.0)7 (41.2)2 (50.0)Raynaud´s phenomen, n (%)1 (25.0)8 (47.1)1 (25.0)Skin involvement, n(%)2 (50.0)10 (58.8)4 (100)Treatment, n(%)Glucocorticoids4 (100)16 (94.1)4 (100)Immunosuppresants4 (100)16 (94.1)4 (100)Biological therapy1 (25.0)8 (47.1)2 (50.0)Drug´s number (mean, SD)3 ± 0.85 ± 2.94.7 ± 1.8Antisynthetase antibodies, n(%)Anti Jo13 (75.0)15 (88.2)4(100)PL70 (0)1 (5.9)0 (0)PL121 (25.0)1 (5.9)0 (0)Ro523 (75.0)14 (82.4)2 (50.0)RF positive1 (25.0)4 (23.5)1 (25.0)CK increase2 (50.0)11 (64.7)4 (100)Aldolase increase2 (50.0)12 (70.6)4 (100)Functional respiratory tests: mean(CI95%)Variation DLCOc(%)-4.4 (-12.5, 3.7)-2.5(-6.1, 1.0)7.4 (-10.6, 25.3)Variation FVC(%)-1.1 (-12.8, 9.1)6.0 (3.2, 8.8)7.5 (-9.5, 24.6)Variation FEV1(%)0 (0-2.25)5.0 (1.9, 8.3)7.35 (-18.0, 32.7)Variation FEV1/FVC(%)0.5 (-7.1, 8.2)-1.3 (-2.22, -0.37)-0.4(-12.88, 11.98)Conclusion:ILD is a frequent and serious manifestation that can occur in patients with antisynthetase syndrome, which may have different radiological patterns. In our series, the most observed radiological pattern has been the NSIP pattern with 68%. The pattern most associated with the Ro 52 antibody was the UIP pattern and the NSIP pattern. As for the group that required the largest numbers of drugs (including biological therapy) it was the NSIP pattern. When evaluating changes in respiratory function tests, the pattern that shows a tendency to improve over time is organized pneumonia with improvement of the DLCO, FVC, FEV1, FEV1 / FVC, while the UIP pattern showed a worsening of the DLCO and the FVC.Disclosure of Interests:None declared

Background:ASSD is characterized by antisynthetase antibodies (ARS) and the triad arthritis/myositis/Interstitial Lung Disease (ILD). ASSD and systemic sclerosis (SSc) may share features, like Raynaud’s phenomenon (RP), capillaroscopic alterations, and also some SSc specific autoantibodies.Objectives:To evaluate the characteristics of ASSD + for anticentromere antibodies (ACA).Methods:Retrospective analysis of clinical and laboratory characteristics of ACA + ASSD. Patients were identified in an established international cohort, randomly matched 1:1 for sex, age, disease duration and ARS positivity with a group of ACA - ASSD.Results:18 ACA + ASSD (15 females, 83%, 15 anti-Jo1, 2 anti-PL7, 1 anti-PL12 ARS) patients were identified. In comparison to ACA - group, no differences were observed in disease clinical presentation and evolution. Though, 9 ACA + patients (50%) satisfied the ACR/EULAR 2013 classification criteria for SSc and only 1 in ACA - group (p=0.007) (Table 1).An incomplete ASSD (lack of at least one triad finding) was observed in 15 patients in both ACA + and – group (p=1). Among these patients, 13 ACA + and 11 ACA – developed de-novo triad finding during disease course (p=0.651). In ACA + group, a de-novo arthritis was observed in 4 patients (vs 1, p=0.565), a de-novo myositis in 8 (vs 5, p=1), and a de-novo ILD in 7 (vs 10, p=1). The prevalence of complete forms was similar between ACA + and – group at both disease onset (3 vs 3, 17%, p=1) and last follow-up, (10 vs 11, 56% vs 61%, p=1). Of note, only 1 patient (6%) for each group died (p=1).Conclusion:The clinical spectrum time course of ACA+ and - ASSD is similar, even when ACA + patients could be classified as SSc. By considering the high prevalence of arthritis and myositis we observed, we suggest that ACA+ patients with arthritis and myositis, should be tested for ARS antibodies even when an ASSD is not clearly suspected.References:[1]Mirrakhimov AE. Curr Med Chem 2015;22:1963–75[2]Cavagna L. J Clin Med 2019;8:E2013[3]Sebastiani M. J Rheum 2019:46:279-84[4]van den Hoogen F. Ann Rheum Dis 2013;72:1747-55Table 1.Patients characteristics. IQR, interquartile range; ILD, interstitial Lung Disease; SSc, systemic sclerosisACA+ (18)ACA - (18)pAge (years) at disease onset (median, IQR)47 (37-63)47 (39-63)0.834Disease duration (months) (median, IQR)81 (62-169)77 (58-165)0.486anti Ro52antibody (%)12(67)11 (61)1Arthritis onset10 (56)13 (72)0.489Arthritis last follow-up (%)14 (78)14 (78%)1Myositis onset (%)7 (39)11 (61)0.318Myositis last follow-up (%)15 (83)16 (89)1ILD onset (%)9 (50)6 (33)0.5ILD last follow-up (%)16 (89)16 (89)1Complete form onset (%)3 (17)3 (17)1Complete form last follow-up (%)10 (56)11 (61)1Raynaud phenomenon (%)13 (72)9 (50)0.305Mechanic’s hands (%)6 (33)7 (38)1Teleangectasias (%)2 (11)0 (0)0.486Cutaneous sclerosis (%)510.177Acral ulcers (%)1 (6)0 (0)1Scleroderma pattern at NVC8 (44)7 (39)1Pulmonary arterial hypertension (%)3 (17)2 (11)12013 ACR/EULAR SSc classification criteria9 (50)1 (6)0.007Disclosure of Interests:Giovanni Zanframundo: None declared, Gianluca Sambataro: None declared, Veronica Codullo: None declared, Alessandro Biglia: None declared, Emanuele Bozzalla Cassione: None declared, Elena Bravi: 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, Marco Fornaro: None declared, Konstantinos Triantafyllias: None declared, Alberto Pesci: None declared, Paola Tomietto: None declared, Øyvind Molberg: None declared, Salvatore Scarpato: None declared, Reinhard Voll: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Bristol-Myers Squibb, Speakers bureau: Acetelion, Lilly, Boehringer Ingelheim, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Carlomaurizio Montecucco: None declared, Lorenzo Cavagna: None declared

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:Antisynthetase syndrome (AS) may have different clinical phenotypes and outcomes associated with different anti-aminoacyl RNA-synthetase (anti-ARS). Patients may also present with incomplete/early phenotypes that do not fulfil the classification criteria.Objectives:To evaluate the clinical and demographic characteristics of patients positive for anti-ARS in our Myositis clinic.Methods:Observational study using data from the Portuguese Rheumatic Diseases Register (Reuma.pt/Myositis protocol). Data extracted included demographic variables, clinical features and immunological expression of the disease.Results:17 patients were identified. All met the criteria for AS according to Connors criteria, while 3 did not met according to the Solomon criteria. Mean age at diagnosis was 60.1 years (26 - 80) and 76.5% were female. Mean follow-up time was 2.8 (0.5-9) years. Only 3 patients had history of smoking in the past. The autoantibodies expressed were anti-Jo1 (n=12), anti-PL12 (n=2), anti-OJ (n=2) and anti-PL7 (n=1). 4 patients positive for anti-Jo-1 also expressed anti-Ro52. The clinical information and treatment are described in table 1. One patient presented as a paraneoplastic syndrome associated with anti-Jo-1.Table 1.Demographic and clinic characteristics of our cohort. AZA – azathioprine; CYC – Cyclophosphamide; DM – dermatomyositis; GS – Gottron’s sign; ILD – Interstitial lung disease; PM – Polymyositis; NSIP - Nonspecific interstitial pneumonia; MH – mechanic hands; MMF - Mycophenolate mofetil; MTX – Methotrexate; PDN – prednisolone; RP – Raynaud phenomenon; RTX – Rituximab; UIP - Usual interstitial pneumonia; Y – yes; N – no. Connors criteria – anti-ARS plus one or more of RP, MH, arthritis, ILD, fever. Solomon criteria – anti-ARS plus 2 major criteria or 1 major and 2 minor criteria. *induction therapy.CaseSerologyMajor criteria (ILD [NSIP/UIP/non-specific] or PM/DM)Minor criteria (Arthritis, MH, RP)Other manifestationsConnors (2010)/ Solomon (2011) criteriaPDNDMARDcs (MTX/MMF/AZA)CYC/RTX1Jo1PMMH, arthritisGSY/YYMMF-2Jo1NSIPRP, MHAstheniaY/YYAZA-3Jo1NSIPMH, arthritisCalcinosis, astheniaY/YYAZA-4Jo1NSIP; DM-GSY/YY--5Jo1/Ro52PMMH, arthritisGS, astheniaY/YYMTX-6Jo1UIPRP, arthritisAstheniaY/YY-RTX7Jo1/Ro52NSIP; PMarthritis-Y/YYMMFCYC*8Jo1NSIP; PM--Y/YYMMF-9Jo1/Ro52NSIP; PM--Y/YYAZA-10PL7-RP, arthritis, MHDysphagiaY/NY--11Jo1-RPAstheniaY/N---12Jo1/Ro52PMMH, arthritisGS, astheniaY/YYMMF-13PL12PMRP, arthritisGS, astheniaY/YYMMF-14Jo1UIPRP, arthritisWeight loss, astheniaY/YY-RTX15OJNon-specific pattern--Y/NYMMF-16OJNSIP--Y/YY--17PL12PMRP, MH-Y/Y---Conclusion:The most frequent autoantibody was anti-Jo-1, which is consistent with the literature. Interestingly, patients with anti-PL, usually described as having severe lung disease, in our series do not have it. Additionally, we found a trend for a younger age at diagnosis in Jo1 positive patients and remarkably more than half of these patients have been diagnosed with ILD, being the NSIP pattern the most frequently reported.Disclosure of Interests:None declared

Background:Antisynthetase Syndrom (ASyS) is an autoimmune overlap disease characterized by antiaminoacyl-tRNA-synthetase (anti-ARS) antibodies and the classic triad of arthritis, myositis and interstitial lung disease (ILD) (1). Markers of cardiovascular (CV) or cerebrovascular (CVB) risk have never been examined in ASyS.Objectives:Aim of this study (RIsk of CARdiovascular Disease in ASyS: RI.CAR.D.A.) was to test the ability of an established traditional CV risk prediction score (Systematic Coronary Risk Evaluation-SCORE) and its EULAR modified version (mSCORE) to identify ASyS patients at high CV risk. Moreover, we sought to examine for the first time associations of CV surrogate markers with clinical and immunological ASyS parameters.Methods:SCORE/mSCORE and the gold standard marker of aortic stiffness (carotid-femoral pulse wave velocity-cfPWV) were examined in patients with ASyS and healthy controls in a multicenter setting (6 Rheumatology Centers). Moreover, sonography of the common- (CCA), internal- (ICA) and external- (ECA) carotid arteries was performed in subsets of both groups, evaluating carotid intima-media-thickness (cIMT), plaques and duplex-sonographic indices of CBV risk such as the resistance- (RI) and pulsatility-index (PI).Figure 1.Carotid Doppler surrogate markers of cardiovascular and cerebrovascular risk in controls and ASyS (case).cIMTCarotid intima media thickness;CAA(common-),ICA(internal),ECA(external) carotid artery;RIresistance index;PIpulsatility index. (all;p< 0.05)Results:We recruited 66 ASyS patients with different anti-ARS and 88 controls. According to mSCORE5/50 (10%) of the patients had high CV risk. However, cfPWV and carotid sonography (CS) revealed an increased CV risk in21.2%and subclinical carotid arteriosclerosis (plaques and/or cIMT>0.9 mm) (SCA) in85.7%of the patients respectively. ROC analyses showed similarly poor diagnostic performances of SCORE/mSCORE in comparison to cfPWV(>10 m/s) and SAC by areas under the curve (AUC) of0.56 (95%CI=0.39-0.73) and0.63 (95%CI=0.3-0.96),respectively. cfPWV and SCA were higher in ASyS patients compared to controls (padj=0.021andp=0.003, respectively). cfPWV and cIMT correlated in the patient group significantly with age (r=0.679; prespectively).Moreover, cfPWV correlated with BMI (padj=0.001) and diabetes(padj=0.043). ACC-RI and ACC-PI showed significant associations with a marker of myositis activity [creatine phosphokinase (CPK):r=0.629;p=0.012andr=0.574;p=0.032, respectively]. Finally, ACI-RI and ACI-PI values were higher in patients with ILD (both;p=0.039).Conclusion:This is the first report of higher aortic stiffness and SCA in ASyS patients compared to controls. Active myositis and presence of ILD were associated with higher CVB risk parameters. Furthermore, SCORE/mSCORE performed poorly in identifying patients at high CV risk and carotid arteriosclerosis compared to cfPWV and CS respectively. Thus, cfPWV and CS could improve CV and CBV screening in ASyS patients.References:[1]Cavagna L, et al. Clinical Spectrum Time Course in Anti Jo-1 Positive Antisynthetase Syndrome.Medicine2015;94:1144.Disclosure of Interests:None declared

The presence of muscle weakness and anti-Jo1 anti-aminoacyl transfer RNA synthetase (ARS) autoantibodies are evaluated in the new European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) proposed classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM), as well as in the Solomon proposed criteria for antisynthetase syndrome (ASSD) diagnosis.1 2 That favours an overlapping in both criteria fulfilment; however, ASSD is not considered among the IIM subgroups classification. Anti-Jo1 ARS positivity is the highest weighted criterion in the EULAR/ACR criteria. Furthermore, anti-PL7 and anti-PL12 ARS were found to be strongly associated with IIM during the criteria development; however, the low number of observations limited their reliability analysis, and they were not finally included.1 3 Anti-EJ, anti-OJ and other ARS were not considered at all due to the limited availability of detection methods at the start of the criteria development.3 On the other hand, any ARS positivity is considered in Solomon’s criteria. Thus, according to other authors, we purpose that IIM and ASSD classification criteria …

We have recently published a retrospective two centres study of 37 patients with clinical suspicion of idiopathic inflammatory myopathies (IIM) or antisynthetase syndrome (ASSD), and antiaminoacyl-transfer RNA synthetase (ARS) autoantibodies in the myositis immunoblot. In it, we discussed the role of the ARS in the IIM and the ASSD classification criteria, and a possible overlapping between both of them.1 Regarding the detection of ARS, previous studies have shown differences in the specificity between different commercial assays; thus, in agreement with the highly appropriate commentaries raised by Knitza et al on our report, we consider that a careful interpretation of them is mandatory.2 3 In this way, in a recent review Damoiseaux et al proposed that to safeguard a high specificity of myositis-specific autoantibodies in multispecific-assays, it could be useful1: to establish adequate cut-off values in the immunoblot2; to correlate the results with another monospecific-assay (ie, ELISA …

We have with great interest read the letter entitled ‘Response to: ‘Idiopathic inflammatory myopathies and antisynthetase syndrome: contribution of antisynthetase antibodies to improve current classification criteria’ by Greco et al ’ by Knitza et al , to be published in the Annals of the Rheumatic Diseases .1 We appreciate the thoughtful comments made by the authors and agree on the importance of aminoacyl transfer RNA synthetase (ARS) autoantibodies, as well as other autoantibodies for correct classification of the associated diseases. The discussion stems from the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) …

With great interest, we read the letter titled ‘Idiopathic inflammatory myopathies and antisynthetase syndrome: contribution of antisynthetase antibodies to improve current classification criteria’ by Greco et al 1 published in the Annals of the Rheumatic Diseases . The authors analysed if the detection of anti-aminoacyl transfer RNA synthetase (ARS) autoantibodies other than anti-Jo1 could improve the European League Against Rheumatism/Amercian College of Rheumatology (EULAR/ACR) classification criteria2 for adult and juvenile idiopathic inflammatory …

We report the case of an 80-year-old Caucasian man with PL-12 antibody positive antisynthetase syndrome. He presented with progressive dyspnoea and weight loss, later developing dysphagia, mild proximal muscle weakness and mild sicca symptoms. Investigations revealed interstitial lung disease, inflammatory myopathy and an immunology profile consistent with PL-12 antisynthetase syndrome. Prednisolone and cyclophosphamide resulted in a significant improvement of all his symptoms.

ObjectiveAs rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPAs) are not routinely tested in idiopathic inflammatory myositis (IIM), little is known about their prevalence and clinical implications in this patient group. In antisynthetase syndrome (ASS), presence of ACPA is reportedly associated with more severe and erosive arthritis. We aim to retrospectively determine the prevalence of RF and ACPA in a cross-sectional cohort of 121 patients diagnosed with IIM and to assess clinical associations.MethodsSerum samples from 121 patients diagnosed with polymyositis (n=30), dermatomyositis (n=41), ASS (n=37), inclusion body myositis (n=1), necrotising autoimmune myopathy (n=5) or overlap myositis (n=7) were analysed. RF was evaluated by nephelometry (Immage 800, Beckman–Coulter); anti-CCP antibodies were identified using fluoro enzyme immunoassays (Immuno-Cap 250, Thermo Fisher). Values above 40 IU/mL and 7 U/mL were considered positive for RF and ACPA, respectively.ResultsThe prevalence of RF and ACPA was 9.09% and 4.96%, respectively. No significant differences were observed between RF/ACPA positive versus negative patients. There was a numerical trend for RF-positive IIM patients to be older and have lower forced expiratory volume in 1 s levels.ConclusionsRF and ACPA are prevalent in IIM, although we detected a lower prevalence than reported in previous studies. Presence of these antibodies in patients with IIM patients is not clinically relevant in our cohort.

Objectives:To describe and analyse the manifestation of sclerosing skin disorders in patients with multiple sclerosis (MS).Case reports:We describe three patients with relapsing-remitting MS who developed skin sclerosis while receiving interferon (IFN)-β treatment and review nine further cases of systemic sclerosis (SSc) in MS from the literature. Of all 12 patients reported, eight had limited cutaneous SSc, three had diffuse cutaneous SSc and one patient had an antisynthetase syndrome. Localised scleroderma such as morphoea was not described. The mean age at diagnosis was 25.2 years for MS (range 12 to 51) and 38.3 years for SSc (range 16 to 66). Eleven patients developed SSc after the onset of MS and manifested with skin sclerosis after a mean of 14.9 years (range 1 to 45). In five patients IFN-β was commenced before the development of skin sclerosis (mean 4.6 years, range 1 to 8 years). There was no relationship between the onset of skin sclerosis and MS activity. With the exception of one individual, all patients had antinuclear antibodies.Conclusions:Sclerosing skin disorders may develop in the course of MS. The relatively early age of SSc onset in patients with MS suggests a genetic predisposition and/or an IFN-associated trigger.

We read with great interest the extended report by Lilleker et al 1 on the EuroMyositis registry. Our attention was particularly addressed to antisynthetase syndrome (ASSD) because in the last years we and all members of the AENEAS (American and European Network of Antisynthetase Syndrome) collaborative group strongly contributed2–7 to increase the knowledge on this peculiar disease. We think that a comparison between our cohorts could be of interest and useful for clinicians, even if the lack of some data in the EuroMyositis paper does not allow us to perform statistical analysis. Both groups collected a very large number of patients (AENEAS collaborative group 813 cases, EuroMyositis 512 cases). The comparison of available …

Introduction Idiopathic inflammatory myopathies may be an overlapping disease complex. Although interstitial lung disease affects the mortality and the morbidity of the disease, a clinical course and the prognosis of the disease complicated with interstitial lung disease are diverse among individuals and prognostic factors have yet to be clarified. This article aims to report the rationale and the methodology of a future intended systematic review and meta-analysis of prognostic factors of idiopathic inflammatory myopathies complicated with interstitial lung disease. Methods and analysis Participants are eligible if they are diagnosed as polymyositis/dermatomyositis, clinically amyopathic dermatomyositis or antisynthetase syndrome complicated with interstitial lung disease. Primary outcomes are all-cause and pulmonary-cause mortality and secondary outcomes include a progression of the disease and a deterioration of health-related quality of life. All primary studies of any design aside from case reports or case series are included. 2 reviewers will search electronic databases such as the MEDLINE, the EMBASE and the Science Citation Index Expanded and extract relevant data independently. A risk of bias in individual studies is evaluated based on the Quality in Prognostic Studies tool. Meta-analysis will be conducted if 3 or more studies are available for each outcome and pooled effects will be presented by the odds ratio (OR). Where combining data is inappropriate due to a small number of studies or substantial heterogeneity, the result is reported qualitatively. Subgroup and sensitivity analysis are also considered based on clinical and methodological differences such as clinical manifestations, study designs and the quality of studies. The evidence level is assessed following the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) method. Ethics and dissemination This study raises no ethical issues as it is based on the findings of previously published articles. The result will be reported in a peer-reviewed medical journal. Trial registration number CRD42016036999.

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 Over the last few years, the discovery of myositis-specific antibodies (MSAs) has allowed the characterization, besides the three main entities: polymyositis (PM), dermatomyositis (DM) and inclusions body myositis, of new clinical entities such as the antisynthetase syndrome (ASS) and autoimmune necrotizing myopathy. Objectives The objective of this study was to determine the clinical profile of myositis patients with MSAs. Methods From January 2006 to February 2014, we collected the myositis patients with positive MSAs followed in Internal Medicine Department of “La Rabta” Hospital. Autoantibodies were detected by immunodot (Euroimmun®), to identify anti-Mi-2, anti-SRP and anti-synthetase antibodies (anti-Jo-1, anti-PL-7, anti-PL-12, anti -EJ and anti-OJ). Results We identified 26 patients (22 women) with one or more MSAs. The average age was 44 years. Eleven patients had two MSAs and only one patient had three MSAs. The anti-Mi-2 autoantibodies were positive in 11 cases: 8 cases of DM, 2 cases of PM and one case of ASS. The myopathy was benign in all cases, the oesopharyngeal and respiratory disease was observed in 5 cases and cardiac involvement in one case. The anti-SRP antibodies were positive in 16 cases: 13 cases of DM, 2 cases of PM and one case of ASS. The myopathy was acute onset in 2 cases, the oesopharyngeal disease was observed in 11 cases and the respiratory disease in 9 cases. Cardiac involvement was observed in 2 cases. Anti-Jo-1 antibodies were positive in 9 cases, 7 cases of ASS and 2 cases of DM, the anti-PL-7 antibodies were positive in a case of PM and the anti-PL-12 antibodies were positive in two cases of DM. Anti-EJ and anti-OJ antibodies were negative in all cases. Conclusions Usually, anti-Mi-2, anti-synthetases and anti-SRP antibodies are associated with benign DM, ASS, autoimmune necrotizing myopathy and cardiac involvement respectively. These associations were not confirmed in our study which reflects an atypical profile of MSAs in Tunisian patients. 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 Interstitial lung disease (ILD) is a common cause of morbidity and mortality in connective tissue disease (CTD) (1), particularly in systemic sclerosis, where it is the most common cause of death (2). Despite several immunosuppressive regimes, including intravenous cyclophosphamide, a significant proportion of patients have progressive ILD. Recent evidence has shown that rituximab is an effective treatment in antisynthetase syndrome associated ILD (3) and in treatment refractory connective tissue disease associated interstitial lung disease (CTD-ILD) as rescue therapy (4). Objectives The objective of this study was to investigate patient outcomes when using rituximab for CTD-ILD refractory to standard immunosuppression, in our specialist centre in Sheffield, UK. Methods A retrospective case review was performed on 12 patients who had received rituximab for CTD-ILD. Details of previous treatment, pulmonary function tests, imaging, autoimmune profiles and basic demographic data were collected. Exercise tolerance, symptoms of dyspnoea and percent predicted forced vital capacity (FVC) and percent predicted diffusion capacity of carbon monoxide (DLco) were compared from baseline and six to nine months after receiving rituximab, to assess response to treatment. Results After six months treatment four patients had significant increases in FVC or DLco defined as an increase of ≥10% or ≥15% from baseline respectively, and three patients had stable disease. Five patients showed progressive disease including one patient with diffuse systemic sclerosis who died and one patient with polymyositis who required lung transplantation. A steroid sparing effect was observed, with a median reduction in prednisolone dose of 5mg daily at six months. Conclusions We found that rituximab can be an effective treatment in some patients with progressive CTD-ILD, even in disease refractory to standard treatment with IV cyclophosphamide. Patients with Jo-1 polymyositis were more likely to have a significant response to treatment. Further randomized controlled studies are needed to aid treatment decisions in this patient group to enable clinicians to identify likely responders, to determine if rituximab is as effective as cyclophosphamide and if use in early CTD-ILD will improve patient outcomes. References Castelino FV et al. Interstitial lung disease in connective tissue diseases: evolving concepts of pathogenesis and management. Arthritis Research and Therapy. 2010;12(4):213. Tyndall AJ et al. Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Annals of the rheumatic diseases. 2010 Oct;69(10):1809-15. Sem M et al. Rituximab treatment of the anti-synthetase syndrome: a retrospective case series. Rheumatology. 2009 Aug;48(8):968-71. Keir GJ et al. Severe interstitial lung disease in connective tissue disease: rituximab as rescue therapy. The European respiratory journal. 2012 Sep; 40(3):641-8. Disclosure of Interest None declared

Background Antisynthetase syndrome (ASS) can be a life-threatening condition. Patients with ASS in the context of idiopathic inflammatory myositis (IIM) have been described to have a worse prognosis compared to patients either with dermatomyositis (DM) or polymyositis (PM) alone. Objectives To evaluate survival and mortality in a large cohort of Spanish patients with anti-Jo1 ASS and compare it with mortality rates of Spanish general population. Methods From March 2011 to June 2014 we conducted a national multicentre study, including retrospective and prospective data, among members of the GEAS-IIM Group of the SEMI. Clinicians from 18 Spanish centers participated in the development of a registry of patients with Anti-Jo1 ASS. For data collection a specific electronic database including broad information about demographic and clinical data was developed. Continuous variables were compared by the t-student or non-parametric Mann-Whitney tests when appropriated, while X2 test were used to compare categorical variables. The Kaplan-Meier method and long-rank tests were used to compare survival between groups. The standardized mortality ratio (SMR) was calculated using the Spanish mortality registry. Results were expressed with its 95% interval confiance (IC). Results A total of 148 anti-Jo1 ASS patients, 90 women (60.8%), were included in the study. Mean (SD) age at diagnosis was 50.8 (16) years. Range follow-up was 1.3 to 412 months [mean (SD) 95 (76.4) months], with only 12 patients with a follow-up fewer than 12 months. Fifteen percent of patients had ILD as the unique main ASS clinical manifestation, other 15% had myositis and 69.3% had both ILD and myositis. Thirty seven patients (25%) died after a median follow-up of 70.3 months (range 4.9 – 308 months). The SMR (95%IC) was 4.77 (3.31-6.67). Main causes of death included respiratory failure (6.8%), cancer (6.1%), infection (4.1%), myositis (2.7%) and acute cardiovascular events (1.3%). A directly ASS-related death were considered in 18 patients (46.6%). Estimated survival rate (95% IC) was 87.5% (81.6% - 93.4%) and 75.4% (66.4% - 84.4%) at 5 and 10 years respectively. Median survival rate (95% IC) was 20.3 years (13.8-26.8 years). No difference in survival was found between patients with myositis (DM or PM) and those with ILD without associated myopathy. The presence of cancer (p=0.02) and an advanced age at ASS diagnosis (p Conclusions Mortality in ASS patients is four-fold and a half higher than in the general population. Mortality can be directly attributed to ASS in near a half of the cases. Respiratory failure, cancer and infection are the main causes of death. Estimated survival rate at 10 years is around 75%. References Marie I. Morbidity and mortality in adult polymyositis and dermatomyositis. Curr Rheumatol Rep.2012;14:275-285. Disclosure of Interest None declared

Background The most frequent myositis specific antibody (MSA) in the serum of patients with idiopathic inflammatory myopathies is anti-Jo-1. The presence of anti-Jo-1 define a distinct clinical phenotype, antisynthetase syndrome (ASS), which is characterized by poor prognosis and multiple organ involvement, such as myositis, interstitial lung disease (ILD), non-erosive arthritis, Raynaud9s phenomen, mechanic9s hand, skin rashes, and fever. Objectives The aim of this study was to determine the clinical, serological, laboratory and genetic features of anti-Jo1 positive patients followed by our department. Methods Retrospective analysis of medical records of 49 patients (42 female, 7 male) were reviewed. Anti-Jo-1 titer was detected with enzyme-linked immunosorbent assay. HLA DRB1, DQA1 and DQB1 genotype was determined using commercial sequence-specific oligonucleotide kit. Statistical analysis was performed using Pearson Chi 2 , Fisher exact test, or Spearman correlation. Results The median age at diagnosis was 43±13,28 years (range: 18-70), 48 patients exhibited myositis (98%), 35 ILD (73%), 43 arthritis (88%), 32 Raynaud9s phenomen (65%), 21 fever (43%), 16 mechanic9s hand (33%), 27 skin rash (55%) and 6 dysphagia (12%). We could detect significant correlation between the initial anti-Jo-1 titer and the first CK (R=0,328; p=0,003) and CRP (R=0,374; p=0,016) level. Furthermore anti-Jo1 levels during disease course had significant correlation to the corresponding CK (R=0,497; p Conclusions Our results confirm previously reported data from other centers considering the clinical features of anti-Jo1 positive patients. HLA DRB1*03 positivity was associated with lower CK level but has no influence on clinical or serological features. It seems that anti-Jo1 level might reflect disease activity; ESR, CRP levels, associated fever and anti-SSA positivity at the diagnosis could be considered as prognostic markers. Disclosure of Interest None declared

We report a case of a 72-year-old Caucasian woman with PL-7 positive antisynthetase syndrome. Clinical presentation included interstitial lung disease, myositis, 'mechanic's hands' and dysphagia. As lung injury was the main concern, treatment consisted of prednisolone and cyclophosphamide. Complete remission with reversal of pulmonary damage was achieved, as reported by CT scan, pulmonary function tests and functional status.

Background Interstitial lung disease (ILD) is a serious complication of rheumatoid arthritis (RA) and different systemic autoimmune diseases. A multidisciplinary management allows optimizing handling and can help reducing its high morbidity and mortality. Objectives To describe the characteristics of a cohort of patients with rheumatic disease-associated ILD (RHEU-ILD) controlled in a specific multidisciplinary consultation Pulmonology-Rheumatology, and to evaluate the changes produced by a joint activity on the diagnosis and/or treatment. Methods All patients treated in the multidisciplinary consultation RHEU-ILD from September-2012 to October-2013 were included in the analysis. We collected the following data: origin of the patients, age, sex, diagnosis, debut and duration of the EPID, antibody profile, HRCT pattern, results of pulmonary function tests (PFTs), walking test, bronchoscopy and/or surgical biopsy (when needed), previous and current treatments, and any diagnostic and/or therapeutic change resulting from this consultation. The package SPSS 17.0 was used for descriptive statistics, and quantitative variables were compared using the t-test for paired samples. Results Fifty-four patients were reviewed, 75.9% female, with a mean age of 63.56±15.40 years. Most patients came referred from Rheumatology (74.1%), since the debut of the EPID was after the diagnosis of the rheumatic disease in 50% of cases (33% simultaneous, and only 13% prior). The non specific interstitial pneumonia was the most frequent ILD (51.9%), followed by the usual interstitial pneumonia (UIP, 33.3%). The mean duration of the ILD was 5.49±5.31 years. ILD was associated, in order, to Systemic Sclerosis (24.2%), RA (20.4%), Sjogren (16.7%) and Antisynthetase syndrome (13%). The antibodies more frequently found were the ANA (33.3%), followed by anti-Ro (31.5%), RF (29.6%) and anti-Scl70 (18.5%). As for the PFTs, up to 55.6% of the patients showed a normal pattern, and only 29.6% a restrictive pattern. 22.2% of the patients showed desaturation when performing the walking test. Bronchoscopy was performed in 29 patients, while transbronchial biopsy and surgical biopsy were needed in 22 and 5 patients, respectively. A combined approach led to 4 changes of diagnosis (2 of them after surgical biopsy) and 9 changes of therapy (16.7%). Corticosteroids were the most used treatment (44%), followed by methotrexate (18.5%), rituximab (14.8%) and mycophenolate (9.3%). At follow-up, no significant change was observed on HRCT (72.2%) and/or the PFTs (baseline FVC 92.27% vs. last FVC 88.73%; p Conclusions The existence of a multidisciplinary consultation Pulmonology-Rheumatology can be key in the final diagnosis and/or treatment of our patients with rheumatic disease-associated ILD. A joint effort could help improving the prognosis of these patients. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5614

Background Antisynthetase syndrome (ASS) is a severe variant of idiopathic inflammatory myopathies. Unfavorable prognosis of this disease is associated with interstitial lung disease (ILD). Conventional treatment with glucocorticoids (GC) and cytotoxic drugs often does not provide sufficient improvement in such patients so addition of biologic agents is an interesting possibility. Objectives To assess efficacy and tolerability of rituximab (RTM) in patients with ASS. Methods RTM was administered to the patients admitted to the Institute of Rheumatology from 2009 to 2013. Manual muscle testing (MMT), dyspnea assessment according to NYHA, creatinkinase (CK) and anti-Jo-1 antibodies (anti-Jo-1) assay; forced vital capacity (FVC) and carbon monoxide diffusion capacity (DLCO) were performed at baseline in 17 and every 6 months thereafter in 12 cases. High-resolution computed tomography (HRCT) scanning of the chest at baseline was performed in 18 and after 6-12 months – in 13 patients. Results 18 patients with ASS (16 female and 2 male, medianan age 50 [44;56], medianan disease duration 24 months [7;108]) were included. 14 from them had decreased MMT value and class 1-2 NYHA dyspnea was present in 17. 11 patients were positive for anti-Jo-1 and 8 had elevated CK level. HRCT showed ILD signs (including ground glass opacities) in all cases. FVC 10% improvement in FVC and 6 had >10% better DLCO values. For the rest pulmonary tests results remained stable. 12 months after treatment regression of ground glass attenuation on HRCT was achieved in 6 cases. In 5 patients lung changes remained stable and in 2 – increased. 12 patients were able to decrease GC dose. Most favorable results were achieved in 2 patients with short duration of the disease. 5 severe infections requiring hospitalization developed after treatment with RTM in 4 patients (severe pneumonia in 3, candidosis in 1, and sepsis with meningitis in 1 case). 2 from them died. All these patients received intermediate or high doses of GC. 6 patients had less severe infections (1- bronchopneumonia, 1 – exacerbation of chronic pyelonephritis, 1 – sinuitis, 1 – panaris, 3 – urinary infection and 1 – genital herpes). Conclusions Treatment with RTM allows to control successfully ILD in patients with ASS. The best results can be achieved on early stage of the disease. High disease activity, high and intermediate GC doses and severe ILD should probably be considered as risk factors of severe infections in patients with idiopathic inflammatory myopathies receving RTM. The risk of infection development is highest 2-3 monthes after the first infusion of RTM. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3597

Background Autoantibodies in the inflammatory myopathies identify unique subsets of patients with distinctive clinical features and provide useful diagnostic and prognostic information. However the association of individual autoantibodies with specific muscle biopsy features has rarely been studied. Objectives To characterize muscle biopsy features associated with different autoantibodies in a cohort of patients with inflammatory myopathies from a single-center. Methods Patients from the Johns Hopkins Myositis Center cohort diagnosed with probable or definite dermatomyositis (according to Bohan and Peter criteria) who had both a muscle biopsy read at Johns Hopkins and a known myositis autoantibody were included in the study. For each biopsy, the presence/absence of the following features were recorded: perifascicular atrophy, mitochondrial dysfunction (>5 COX negative fibers), perivascular inflammation, primary inflammation (invasion of non-necrotic fibers by mononuclear cells) and necrotizing myopathy (defined as biopsies with necrosis/degeneration without perifascicular atrophy or primary inflammation). As a complementary analysis, biopsy features of all anti-Jo1 positive patients with either dermatomyositis or polymyositis were compared through Fisher9s exact test. Results 37 patients with dermatomyositis were included in the study (79.5% definite). These included 11 with anti-Jo-1, 7 with anti-Mi-2, 11 with anti-TIF1-γ, 8 with anti-NXP2, and 5 with anti-PM-Scl. Biopsies from anti-Mi-2 positive patients showed frequent perifascicular atrophy (71.4%), perivascular inflammation (85.7%) and primary inflammation (57.1%); biopsies from anti-TIF1-γ positive patients showed frequent perifascicular atrophy (63.3%), mitochondrial dysfunction (55.6%) and perivascular inflammation (72.7%); biopsies from anti-NXP2 positive patients showed frequent perifascicular atrophy (50%) and biopsies from anti-PM-Scl positive patients showed frequent perivascular inflammation (80%) and primary inflammation (60%). Overall, 16.2% of DM patients had a necrotizing myopathy without perifascicular atrophy or primary inflammation. In the complementary analysis 7 Jo-1 polymyositis patients were identified. Biopsy features of anti-Jo1 patients with dermatomyositis and polymyositis were not statistically different (all p>0.05). Conclusions The majority of anti-PM-Scl and anti-Mi-2 patients have primary inflammation, previously considered the hallmark of PM. Most biopsies from anti-TIF1-γ positive patients reveal mitochondrial dysfunction. 16.2% of DM biopsies have necrotizing myopathy. Biopsy features are similar between dermatomyositis and polymyositis in anti-Jo1 positive patients. References Dalakas MC. Muscle biopsy findings in inflammatory myopathies. Rheumatic diseases clinics of North America 2002;28:779-98, vi. Mozaffar T, Pestronk A. Myopathy with anti-Jo-1 antibodies: pathology in perimysium and neighbouring muscle fibres. Journal of neurology, neurosurgery, and psychiatry 2000;68:472-8. Pestronk A. Acquired immune and inflammatory myopathies: pathologic classification. Current opinion in rheumatology 2011;23:595-604. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5508

Background The Antisynthetase syndrome (ASS) has a high frequency of interstitial lung disease (ILD) leading to increased morbidity and thereby needs for aggressive immunotherapy [1]. Objectives To evaluate efficacy and safety with Rituximab-treatment (Rtx) in a cohort of ASS patients with severe lung disease. Methods Patients from a single referral center diagnosed between 1994-2013 with a positive serologic test of antisynthetase antibodies, ILD and/or myositis were defined as ASS (N=109). Patient data and pulmonary function tests (PFT;s) including forced vital capacity (FVC), forced expiratory volume in one second (FEV 1) and diffusing capacity of the lung for Carbon monoxide (DLCO) were retrospectively collected from medical reports. Severe lung disease was defined as FVC 12 months, and serious adverse events (SAE;s) as events requiring hospitalization within three months after the last Rtx-infusion. To evaluate statistical significance (p10 mg daily to

Background Antisynthetase syndrome (ASS) is a rare condition characterized by the presence of one or more of the following clinical features: arthritis, Raynaud9s phenomenon, “mechanic9s hands”, interstitial lung disease and polymyositis, in patients with antisynthetase antibodies which target aminoacyl-tRNA synthetases enzymes, being Anti-Jo1 the most common one. Objectives To investigate the clinical features of ASS at disease onset and their influence on the disease clinical course. Methods 32 consecutive patients diagnose with ASS, were prospectively enrolled between 1988 and 2013. Inclusion criteria consisted of having a positive test for antisynthetase antibodies, regardless of fulfilling classification criteria for other rheumatic diseases. Serological, clinical and demographic features were registered both at clinical onset and during the course of the disease. Anti-synthetase antibodies were determined by LIA or ELISA. Results From 32 patients, 21 (65.6%) were females and 11 (34.4%) were males. Mean age at clinical onset was 47.4 years (SD 18.8) and the mean time of disease course was 11.1 years (SD 10.2). The most common feature at disease onset was arthritis in 50% of the patients (8 of them presenting arthritis>6 weeks), followed by constitutional syndrome (31.3%) and muscular symptoms (25%). Table 1 shows the different clinical features and frequency of occurrence at onset. During the course of disease 28 patients (87.5%) developed musculoskeletal manifestations, 26 (81.3%) arthritis, 21 (65.6%) cutaneous manifestations, 20 (62.5%) interstitial lung disease and 13 (40.6%) Raynaud9s phenomenon. Associations between the presence of Anti-Ro52 and arthritis at disease onset (p=0.009), interstitial lung disease (p=0.002) and low complement levels (p≤0.001) were found. Conclusions In our study, clinical features at onset were very heterogeneous. Patients showed neither all clinical features at the same time nor during the disease course. In our cohort, Anti-Ro52 antibody was associated to both the presence of arthritis at onset and the development of interstitial lung disease, which could be relevant for differential diagnosis and prognosis. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3113

Background Antisynthetase syndrome (ASS) is an idiopathic inflammatory myopathy characterised by the presence of anti-Jo-1 antibodies. Patients usually present with myositis, interstitial lung diseases, and arthritis. Corticosteroid therapy is the first line treatment. With regard to immunosuppressive use, no consensus has been reached. Rituximab has been reported to be successful in treatment of refractory ASS in small case series Objectives We report our experience of using rituximab in refractory ASS by describing the outcome and follow up of 3 cases Methods The case notes of 3 patients (2 males and 1 female; ages: 50, 42, and 54 years), diagnosed with ASS based on positive anti-Jo1 antibodies and muscle biopsy, were analyzed retrospectively. Treatment with several conventional therapeutic agents was tried sequentially over a mean period of 10 months without sustained remission (see Figs. 1, 2 and 3). In view of the refractory nature of their disease, a decision to commence rituximab was made (1000 mg IV, twice, with a 2-week interval). The available follow up periods for the 3 patients are 36 months in 2 patients, and 67 months in 1 patient. Response to treatment was assessed by improvement in muscle weakness & creatinine kinase (CK) levels Results Response to treatment was observed after a period of 4-5 months following treatment with rituximab. This manifested as improvement in symptoms (muscle weakness, joint pain and shortness of breath), & CK levels (see Figs. 1, 2, and 3). In the first patient (Fig. 1) the improvement following the initial treatment with rituximab was sustained for almost 3 years before he required retreatment with rituximab for relapses (relapsed 4 times afterwards over a period of 32 months, with an average of 11 months between relapses). Retreatment with rituximab in the second patient (Fig. 2) who relapsed at 8 and 18 months following the initial treatment resulted in remission 4-5 months later, and eventually he came off immunosupressive therapy. Retreatment with rituximab in the third patient (Fig. 3) who relapsed at 9 months following initial treatment resulted in remission 4-5 months later. She remained well and continued to receive rituximab prophylactically 6-monthly. The 3 patients have been successfully weaned off the higher dose of prednisolone they used to be on prior to treatment with rituximab; the first patient is currently maintained on prednisolone alone (10 mg daily); the second patient was weaned off prednisolone successfully and is currently on no treatment; while the third is maintained on prednisolone 5 mg daily plus methotrexate 25 mg weekly Conclusions This small retrospective case series indicates a beneficial effect of rituximab in ASS refractory to conventional treatment, in keeping with other case series 1,2 . However the response to treatment may take several months. The relapses at an average of 10 months following initial treatment with rituximab coincide with the timing of repopulation. The optimal timing of retreatment and whether prophylactic retreatment with rituximab at time of repopulation should be considered, remain to be defined. References Martha Sem et al. Rituximab treatment of the anti-synthetase syndrome - a retrospective case series. Rheumatology (2009) 48 (8): 968-971. Elien A. M. Mahler et al. Rituximab treatment in patients with refractory inflammatory myopathies. Rheumatology (2011) doi: 10.1093/rheumatology/ker088 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1878

Background Anti-synthetase syndromes (ASS) are a subset of idiopathic inflammatory myositis (IIM). Patients present with varying combinations of myositis, interstitial lung disease (ILD), Raynaud9s phenomenon and arthritis.Anti Jo-1is the prototypical form of ASS.Non Jo-1 forms are increasing being recognized with anti PL-12 syndrome constituting around 2-3% of IIM patients. Data regarding anti PL-12 is rare and most cohorts report a nearly universal presence of ILD as well as infrequent muscle involvement which is mostly subclinical.The aim of this retrospective review was to determine diagnostic utility of various tests in anti PL-12 ASS patients seen in a single centre. Objectives To determine nailfold capillaroscopic findings as well as identify unique laboratory characteristics in patients diagnosed with anti PL-12 ASS. Methods A search was made among the database of all patients seen in the newly instituted department of rheumatology.Patients identified as having anti PL-12 ASS were identified and details recorded. Results Three patients (Two women and one man) were diagnosed with anti PL-12 antisynthetase syndrome in a short span of 7 months. (July 2013 to December 2013). Their clinical and laboratory characteristics are detailed in the table. Mean age of the patients was 44.3 years.(46,36 & 51 yrs) All three patients had a symptom duration of around 1 month. All patients had fever, myalgia and arthralgia, though only the male patient had objective arhtritis.Objective muscle weakness varied from absent to moderately significant, however all patients demonstrated a normal CPK level.MRI (performed in 2 patients) demonstrated significant muscle oedema.Nailfold capillaroscopy demonstrated significantly high number of microhemorrhages and capillary dropouts. There were a number of megacapillaries as well. None of the patients demonstrated Raynaud9s phenomenon.Despite a normal CPK, patients had a high LDH and borderline high ALT/AST.Patients demonstrated a significantly elevated level of inflammatory markers and leucocytosis.They also demonstrated a hyperglobulinemia (absolute or relative to serum albumin level), though there was an absence of reactive thrombocytosis. Conclusions As in previous literature, patients with anti PL-12 ASS in this single centre cohort demonstrated minimal to moderate myositis.Similar to previous literature they demonstrated an elevated serum LDH level though the serum CPK level was uniformly normal.Nail fold capillaroscopic abnormalities and laboratory features of significant systemic inflammation except for absence of reactive thrombocytosis are described for the first time. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5810

Background MCTD is a disorder characterized by serum auto-antibodies directed against ribonucleoprotein and distinct clinical features including: Raynaud9s phenomenon, “puffy hands”, arthritis, pleuritis, pericarditis, myositis, esophageal dysmotility, pulmonary hypertension and interstitial lung disease (ILD) (1). Anti-SSA antibodies are directed to two different antigens (Ro52 or Ro60). The Ro52 antigen, a 52 kDa protein, is a part of the tripartite motif protein (TRIM21) family (2). Recent studies have shown that anti-Ro52 antibodies are associated with ILD in systemic sclerosis (3) but were not found to be associated with ILD in a cohort of anti-Jo1-positive patients with antisynthetase syndrome (4). Objectives To evaluate the association between lung fibrosis and presence of the anti-Ro52 antibody in a well-defined MCTD cohort. Methods 126 patients, 75% female with a mean disease duration of 9.0 years, were included in the cross-sectional nation-wide unselected Norwegian MCTD cohort, and were examined by high-resolution CT (1). The extent and type of lung abnormalities were scored according to the CT criteria of ILD recommended by the Fleischner Society (5) with reticular patterns consistent with lung fibrosis (1). Serum samples were accessible in 113/126 (90%). The presence of anti-Ro52 and anti-SSB by line immunoassay (ANA Profile 5 Euroline Blot test kit, Euroimmun, Lubeck, Germany). Statistical analyses were performed by SPSS/PASW version 20. Differences between groups were tested by Mantel-Haenszel chi square or Fisher9s exact test with two-tailed 95% significance. Results 57.6% (95%CI; 40.8% to 72.8%) of the MCTD patients with positive anti-Ro52 antibody had lung fibrosis and the risk (odds ratio) was 2.42 higher (95%CI; 1.49 to 3.96) than in those without the antibody. 76.3% (95%CI; 65.8% to 84.3%) of the MCTD patients without the presence of anti-Ro52 did not have lung fibrosis. Conclusions In MCTD, anti-Ro52 antibodies may be a marker of ILD. As this is a cross-sectional study and the patients could develop ILD in time, the study would probably underestimate the predictive value of positive Ro52 antibody. References Gunnarsson R et al. Prevalence and severity of interstitial lung disease in mixed connective tissue disease: a nationwide, cross-sectional study. Ann Rheum Dis. 2012;71(12):1966-72. Rhodes DA et al. The 52 000 MW Ro/SS-A autoantigen in Sjogren9s syndrome/systemic lupus erythematosus (Ro52) is an interferon-gamma inducible tripartite motif protein associated with membrane proximal structures. Immunology. 2002;106(2):246-56. Hudson M et al. Clinical significance of antibodies to Ro52/TRIM21 in systemic sclerosis. Arthritis Res Ther. 2012;14(2):R50. Marie I, et al. Short-Term and Long-Term Outcome of Anti-Jo1-Positive Patients with Anti-Ro52 Antibody. Semin Arthritis Rheum. 2012;41(6):890-9. Hansell DM et al. Fleischner Society: glossary of terms for thoracic imaging. Radiology. 2008;246(3):697-722. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4660

Background Interstitial lung disease (ILD) is a heterogeneous group of disorders that are classified together because of similar clinical and radiographic manifestations. However, prognosis and therapeutic response are influenced by the presence of an underlying cause. Objectives The aim is to study the etiologic profile of ILD in internal medicine. Methods A retrospective analysis of patients with ILD hospitalized in internal medicine department of military hospital from 2000 to 2013. Results We evaluated 44 patients (30 women, 14 men) with a mean age of 57 years. Among them, 32% were smokers. The most common symptom was progressive dyspnea occurring in 83% of cases. All the patients had abnormal chest radiographs, mainly confluent reticular infiltrates or diffuse reticulonodular shadowing. Pulmonary function tests were restrictive in pattern in 54% of the subjects. The most frequent disease was connective tissue disorders (CTD) - associated ILD (64% of all cases): Sjogren9s syndrome (20%), systemic sclerosis (16%), systemic lupus erythematosus (11%), rheumatoid arthritis (9%), antisynthetase syndrome (5%) and dermatomyositis in one case. The diagnostic of both CTD and ILD was made at the same time in 57% of cases. ILD induced by drugs was observed in 16% followed by sarcoidosis in 11% of cases. Idiopathic pulmonary fibrosis was observed in 3 cases and Churg–Strauss syndrome in one case. Corticosteroid therapy was prescribed in 68% of variable dosage depending on the cause and severity of lung disease. Immunosuppressive treatment with cyclophosphamide was indicated in only 4 cases. The response to therapy was favorable in 48% of cases and not satisfactory in 25% of the cases. Conclusions Collagen and vascular diseases are more common than previously appreciated. A multi-disciplinary evaluation of patients with DPLD can enhance diagnosis, improve prognosis and quality of care. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2378

Antisynthetase syndrome was first described by Marguerie et al as a combination of polymyositis (or at least creatine kinase elevation), diffuse interstitial lung disease and autoantibodies to t-RNA synthetase.1 Joint signs and symptoms occur in up to 90% of patients with polymyositis or dermatomyositis2 and/or antisynthetase syndrome, occasionally as the initial manifestations. They include arthralgia, polyarthritis and deforming arthropathy with subluxation. To establish a multicentre registry of patients with joint manifestations of antisynthetase syndrome, a standardised form was posted on the CRI (Club Rhumatismes et Inflammation) website (http://www.cri-net.com), which is part of the French Society for Rheumatology, with the partnership of the French Society of Internal Medicine. During a …

The presence of autoantibodies directed against aminoacyl tRNA synthetases in the sera of patients with idiopathic inflammatory myopathy defines a specific clinical subset that has been called antisynthetase syndrome.1 The prognosis of these patients is conditioned by the increased incidence of interstitial lung disease compared with other types of myositis.2 We report a case of antisynthetase syndrome treated successfully with rituximab. A 57 year old white woman had a 2 month history of painful synovitis of both hands, typical lesions of mechanic’s hands, and moderate proximal muscle weakness. Her laboratory evaluation showed a raised erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and muscle enzymes. Electromyography findings were consistent with the diagnosis of inflammatory myopathy. Prednisone 30 mg/day was immediately started with a good response and then progressively tapered to 10 mg/day. After 3 months, she had a relapse with increased muscle enzyme levels and worsening of articular symptoms, …

Background Lung involvement is common in patients with Rheumatoid Arthritis (RA), including interstitial lung disease (ILD), pleural disease and small airway disease. There are no full reports in the literature analyzing the influence of Rituximab (RTX) in patients with RA with pre-existing lung disease, although it is a rising question in daily clinical practice. Objectives We aim to evaluate the safety and efficacy of RTX in our cohort of RA patients with pre-existing lung involvement. Methods Retrospective observational study of the RA cohort treated with RTX at University College Hospital, identifying patients treated with RTX with any lung involvement. Data were collected on type of lung disease, mortality, respiratory infections and stabilization/progression of symptoms. Results 264 patients with RA have received RTX in our unit between 1998 and 2012. A total of 38 patients (14%) had lung involvement, 24 of them (63%) were female, mean age was 64 years (range 37-79), mean disease duration was 19 years (range 3-42), mean number of RTX cycles was 4 (range 1-10), total follow up duration was 146.7 patient years (median 2.5 years, range 0.5-13.5). 19 of them (50%) had ILD: 3 usual interstitial pneumonitis (UIP), 5 nonspecific interstitial pneumonitis (NSIP, 2 of those had an overlap antisyntetase syndrome), 4 organizing pneumonia (OP) and 7 undetermined ILD. 15 patients (40%) had bronchiectasis. The remaining 4 patients had diagnosis of chronic obstructive pulmonary disease (COPD), small airway disease, pleural effusion requiring decortication and pleural plaques. 6 of the above patients had concomitant COPD. Lung disease has remained clinically and radiologically stable in most patients. One patient with severe UIP before RTX showed slow lung progression over 4 years of follow up, and Mycophenolate mofetil is being considered. The 2 patients with antisynthetase syndrome have stable NSIP but on combination therapy (1 azathioprine, 1 mycophenolate mofetil). 25 patients (66%) reported respiratory infections but in only 6 of these patients was an increased frequency of infections after starting rituximab treatment noted. 2 of these 6 patients had low serum immunoglobulins (1 IgG only, 1 IgG and IgM). 2 patients had serious infections requiring hospitalization. There were 2 deaths, both in patients with bronchiectasis and multiple comorbidities, none directly related to rituximab treatment. Conclusions RTX seems to be a relatively safe therapy in the cohort of RA patients with lung involvement. There is no definite evidence for improvement in lung involvement in RA patients treated with rituximab, but nor there is data suggesting that RTX can lead to a progression of lung symptoms. Only one patient with severe UIP before RTX showed lung progression after 4 years of follow up. Disclosure of Interest: E. Becerra: None Declared, G. Cambridge: None Declared, M. Leandro Grant/research support from: GSK, Abbott., Consultant for: Roche, Chugai

Background The clinical meaning of anti-citrullinated peptide antibodies (ACPA) in antisynthetase syndrome (ASS) is unknown. Methods ASS patients with ACPA were identified among a 9 French center series of 284 patients with ASS and through declarative cases from clinicians registered on the Club Rhumatismes et Inflammation web site. ASS was defined by the presence of an antisynthetase antibody (ARS) and at least two organ involvements among interstitial lung disease (ILD) (abnormal pulmonary function tests and/or typical thoracic HRCT-scan), myositis (muscle weakness, CK level >2 times normal range, myopathic changes on EMG and/or typical features on biopsy) and typical skin manifestations. ACPA were positive when >30 IU/ml (ELISA and/or LUMINEX). Results Eleven female and two male (median age of 43 years, range 23-57) were tested positive for ACPA (median serum amount 183 IU/ml, range 33-7742). ARS were anti-Jo1 (n=10), anti-PL7 (n=2) or anti-PL12 (n=1) and were identified concomitantly (n=10), 4 years before (n=1) or 3-6 years after (n=2) the ACPA detection. Rheumatoid factor (latex) was found in 11 patients (213 IU/L, range 16-925). Among the tested patients, HLA-DR4 allele was found in one case. All patient suffered of symetrical arthritis, involving mainly small joints of the hand (n=13) sparing distal interphalangeal (IP) joints (n=12), with 9 tender joints (range 4-24) and 5.5 swollen joints (range 2-18). The visual analogic pain scale was 60/100, ranging from 20 to 66. Bone erosions were found in 10 patients (78%), mainly on metacarpophalangeal (n=6), metatarsophalangeal (n=4), wirst (n=4) and proximal IP (n=3) joints. All patients presented with at least 2 other symptoms of ASS: - ILD (n=11), occurring prior to (n=3, 2-5 years), at the same time of (n=4) or after (n=4, 1-6 years) the detection of ACPA, with variable severity (vital capacity 94% (range 44-100) and DLCO 67 % (range 48-103). HRCT findings were systematically in accordance with non-specific interstitial pneumonia. - Myositis (n=11) was diagnosed 5-11 years before (n=3), concomitantly (n=5) and 1-3 years after (n=3) the ACPA detection. Muscle weakness was present in 10 patients and the median CK level was 1807 UI/L (range 245-11,434). - Skin manifestations (n=9) were mechanic’s hand (n=3), signs of dermatomyositis (n=4) and/or Raynaud’s phenomenon (n=7) that appeared 1- 2 years before (n=3), concomitantly (n=3) or 3 years after (n=1) the detection of ACPA. All patients received corticosteroids while eleven were treated with DMARDs : methotrexate (n=11), leflunomid (n=1), plaquenil (n=1), mycophenolate mofetil (n=2), Azathioprine (n=1). Seven patients received biologics because of refractory arthritis, including rituximab (n=4), infliximab (n=3), adalimumab (n=1), etanercept (1), tocilizumab (n=1) and/or abatacept (n=1). Other treatments were intraveinous immunoglobulins (n=1) and cyclophosphamide (n=1). Conclusions In ASS, ACPA are associated with severe and erosive arthritis, whereas the prognosis of the other specific ASS involvements seems good. Disclosure of Interest : None Declared

Background Anti-Jo-1 has been negatively associated with cancer. Accordingly, only few reports described the co-existence of anti-Jo-1 positive myositis and malignancy. Despite the apparent rarity of this association, Jo-1 has been shown to be over express by a variety of tumors and it has been proposed that this could lead in some cases to tolerance breakdown. Methods We retrospectively determined the frequency of cancer-associated myositis (CM) in a cohort of 20 anti-Jo-1 positive myositis diagnosed between January 1st 1994 and January 1st 2011 at the Strasbourg University Hospital were reviewed. CM was defined as cancer occurring within the 3 years of myositis diagnosis and, if the cancer is cured, the cure of the myositis as well (as per the modified Bohan and Peter classification of Troyanov et al. (6). To better address the question of a fortuitous or a paraneoplasic link between cancer and anti-Jo-1 positive myositis, we assessed the expression of Jo-1 in available tumor and healthy tissues by immunohistochemistery with monoclonal anti-Jo-1 antibody (Abcam). Results A CM was diagnosed in one patient (5%). A 55 year old woman, smoker, presented a antisynthetase syndrome complicated with myocardial injury. After 3 solumedrol bolus, oral corticosteroids (1.5 mg/kg/day), mycophenolate mofetil (2 g/d) infusion of rituximab (1g) and an infusion of immunoglobulins (2 g/kg), evolution was only mildly favorable. Concomitantly, a nodule of the right breast was found, the biopsy revealed an infiltrating ductal carcinoma. There was no other location. Right mastectomy was performed, followed by chemotherapy, radiotherapy and hormone therapy. Within 4 weeks following surgery, the symptoms disappeared dramatically. 6 months after the mastectomy all immunomodulatory therapy, including corticosteroids, was stopped. 1 year after stopping treatment, myositis was still in remission. Immunohistochemical study of the specimen showed an overexpression of Jo-1 in the cytoplasm of tumor cells compared to normal cells. Conclusions It cannot be ruled out that chemotherapy had an immunomodulatory effect by itself on myositis. anti-Jo-1 myositis were characterised by a chronic course and all patients relapsed within the year following the steroid taper to 5mg or less (7). One year and half after the stop of cortiocosteroids therapy, our patient myositis was still in remission. Moreover, Jo-1 antibodies disappeared. All together, these data suggest that anti-Jo-1 positive myositis was an authentic paraneoplasic syndrome in this patient. For the first time, we studied expression of Jo-1 antigen in a patient with anti-Jo-1 positive CM. Immunohistochemistery assays showed that Jo-1 was over expressed in tumor cells. This result corroborates the hypothesis of a triggering role of the tumour on autoimmune process. The positivity of Jo-1 antibodies may not be an exclusion criterion for the diagnosis of cancer-associated myositis. A thorough age-appropriate malignancy work up may be indicated in all patients with a new diagnosis of myositis, despite the presence of anti-Jo-1 antibodies. Disclosure of Interest None Declared

We read with interest the manuscript by Aggarwal et al 1 entitled ‘ Patients with non-Jo-1 anti-RNA-synthetase autoantibodies have worse survival than Jo-1 positive patients ’. This large cohort study provides important information on outcomes for patients with antisynthetase syndrome (ASS), based on the specificity of the anti-RNA-synthetase autoantibody subtypes. Interestingly, the authors decided to include patients with anti-glycyl (EJ), anti-isoleucyl (OJ) and anti-asparagyl (KS)-tRNA-synthetase autoantibodies, something which had not yet been done in the previous studies,2 ,3 due to …

Background The therapeutic indications for rituximab are: Hodgkin9s lymphoma, chronic lymphocytic leukaemia and rheumatoid arthritis. Purpose The aim of this study was to review the off-label use of rituximab in our hospital. Materials and methods Retrospective study of rituximab in off-label indications from October 2009 to June 2011. Data collected: age, sex, diagnosis, posology, number of doses planned and administered and cost of treatment. Results Rituximab was used for 21 patients (76.1% women) with a mean age of 39.3 years (11-71). The indications were antisynthetase syndrome (dermatomyositis), autoimmune encephalitis, nephrotic syndrome, neoplastic cerebellar syndrome, pemphigus foliaceus, acquired haemophilia A, acute renal rejection (2), autoimmune thrombocytopenic purpura (ITP) (2), systemic lupus erythematosus (SLE) (5) and neuromyelitis optica (6). Posology varied according to the indication. SLE and antisynthetase syndrome: 1 g every 14 days, 2 doses. Nephrotic syndrome, ITP, pemphigus foliaceus, haemophilia A and neuromyelitis optica: 375 mg / m2 intravenous once weekly, 4 doses and in the last indication there is an option of retreatment with 2 doses of 1000 mg depending the CD19 count. Neoplastic cerebellar syndrome: 375 mg/m2 intravenous every 28 days, 4 doses. Acute humoral rejection: 500 mg (single dose) for 1 patient once weekly, 4 doses for the other patient. 14.2% of patients didn9t start treatment with rituximab and 72.2% received the planned total doses. Only 1 patient received 2 doses as a retreatment for neuromyelitis optica. The off-label use of rituximab meant a cost of 90,638 €. Conclusions Rituximab is widely used in autoimmune pathologies as a therapeutic alternative in patients who have failed conventional treatment, although its use is not supported by large clinical trials. The high cost and its wide use warrant large randomised controlled clinical trials to demonstrate its efficacy.