Brachio-cervical inflammatory myopathy associated with systemic sclerosis. Case series and review of literature

This study was aimed at describing a case series of brachio-cervical inflammatory myopathy (BCIM) associated with systemic sclerosis (SSc), due to its rarity and limited coverage in published data. Another aim was to provide a literature review. We reported four cases of BCIM-SSc from our tertiary center. In addition, we researched the literature and found six articles featuring 17 patients who fit this phenotype. We pooled all cases and reported their features. Most patients were female and had limited SSc, and the median time of BCIM presentation was three years after SSc diagnosis. Asymmetric muscle involvement, scapular winging, dropped head, axial weakness, camptocormia, dysphagia, and dermatomyositis stigmas were common features. All patients had esophageal involvement. Most had positive antinuclear antibody results, a scleroderma pattern in their capillaroscopy images, elevated serum creatine phosphokinase, myopathic electrophysiology, and muscle involvement in magnetic resonance imaging. Muscle histopathological findings varied widely, but in general all showed the presence of lymphoid infiltrates, muscle atrophy, increased MHC-I expression, MAC deposits, vasculopathy, and muscle fiber necrosis. The response to immunosuppressive therapy was highly irregular. BCIM-SSc is a rare disorder that shares many similar phenotypes among the described cases, but has a highly heterogeneous response to treatment. At present, more data on the physiopathology, clinical features, and treatment is still needed.

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Thrombospondin-1 mediates muscle damage in brachio-cervical inflammatory myopathy and systemic sclerosis

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000000694 ◽

2020 ◽

Vol 7 (3) ◽

pp. e694 ◽

Cited By ~ 4

Author(s):

Xavier Suárez-Calvet ◽

Jorge Alonso-Pérez ◽

Ivan Castellví ◽

Ana Carrasco-Rozas ◽

Esther Fernández-Simón ◽

...

Keyword(s):

Systemic Sclerosis ◽

Muscle Biopsy ◽

Transforming Growth Factor ◽

Immunosuppressive Treatment ◽

Inflammatory Myopathy ◽

Response To Treatment ◽

Muscle Involvement ◽

Thrombospondin 1

ObjectiveTo describe the clinical, serologic and histologic features of a cohort of patients with brachio-cervical inflammatory myopathy (BCIM) associated with systemic sclerosis (SSc) and unravel disease-specific pathophysiologic mechanisms occurring in these patients.MethodsWe reviewed clinical, immunologic, muscle MRI, nailfold videocapillaroscopy, muscle biopsy, and response to treatment data from 8 patients with BCIM-SSc. We compared cytokine profiles between patients with BCIM-SSc and SSc without muscle involvement and controls. We analyzed the effect of the deregulated cytokines in vitro (fibroblasts, endothelial cells, and muscle cells) and in vivo.ResultsAll patients with BCIM-SSc presented with muscle weakness involving cervical and proximal muscles of the upper limbs plus Raynaud syndrome, telangiectasia and/or sclerodactilia, hypotonia of the esophagus, and interstitial lung disease. Immunosuppressive treatment stopped the progression of the disease. Muscle biopsy showed pathologic changes including the presence of necrotic fibers, fibrosis, and reduced capillary number and size. Cytokines involved in inflammation, angiogenesis, and fibrosis were deregulated. Thrombospondin-1 (TSP-1), which participates in all these 3 processes, was upregulated in patients with BCIM-SSc. In vitro, TSP-1 and serum of patients with BCIM-SSc promoted proliferation and upregulation of collagen, fibronectin, and transforming growth factor beta in fibroblasts. TSP-1 disrupted vascular network, decreased muscle differentiation, and promoted hypotrophic myotubes. In vivo, TSP-1 increased fibrotic tissue and profibrotic macrophage infiltration in the muscle.ConclusionsPatients with SSc may present with a clinically and pathologically distinct myopathy. A prompt and correct diagnosis has important implications for treatment. Finally, TSP-1 may participate in the pathologic changes observed in muscle.

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FRI0236 FIRST PILOT STUDY OF T1 MAPPING MRI WITH ECV MEASUREMENT OF PERIPHERAL MUSCLE IN SYSTEMIC SCLEROSIS PATIENTS SHOWS DIFFUSE FIBROSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5724 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 702.2-702

Author(s):

R. B. Dumitru ◽

A. Goodall ◽

D. Broadbent ◽

A. Kidambi ◽

S. Plein ◽

...

Keyword(s):

Skeletal Muscle ◽

Systemic Sclerosis ◽

Pilot Study ◽

T1 Mapping ◽

Inflammatory Myopathy ◽

Extracellular Volume ◽

Diffuse Fibrosis ◽

Muscle Involvement ◽

Native T1 ◽

Peripheral Muscle

Background:Peripheral myositis in systemic sclerosis (SSc) is associated with poor prognosis and myocarditis1but non-inflammatory myopathy, which also represents a significant cause of disability in SSc remains poorly understood. Cardiovascular magnetic resonance (CMR) T1 mapping studies in asymptomatic SSc patients show increased extracellular volume (ECV), suggestive of diffuse fibrosis in both the myocardium and thoracic muscle2.Objectives:To evaluate the feasibility of T1 mapping MRI and determine ECV in peripheral muscle of SSc patients with and without myopathy and explore the association between cardiac and peripheral muscle T1 mapping in SSc.Methods:This was a hypothesis-generating pilot and feasibility study. SSc patients, fulfilling the 2013 ACR/EULAR criteria, with no cardiovascular disease or myositis but either minimal muscle symptoms (non-inflammatory myopathy) or no muscle involvement and healthy volunteers (HV) underwent peripheral muscle T1 mapping-MRI for native T1 and extracellular volume (ECV) quantification of the dominant thigh. Patients also had T1 mapping CMR, and creatine-kinase (CK) measured. Non-inflammatory myopathy was defined as current/history of minimally raised CK (<600 IU/l) +/- presence of clinical signs-symptoms (including proximal myasthenia and/or myalgia) +/- a Manual Muscle Testing (MMT) score <5 in the thighs.Results:12 SSc patients and 10 HV were recruited. SSc patients had a median (IQR) age of 52 (41,65) years, 9/12 had limited cutaneous SSc, 4/12 interstitial lung disease, 7/12 non-inflammatory myopathy. Higher skeletal muscle ECV was recorded in SSc patients compared to HV [mean (SD) 23(11)%, vs 11(4)% p=0.04]. Skeletal muscle native T1 values were comparable between the 2 groups although modestly higher in SSc patients [mean (SD) 1396ms (56) vs 1387ms (42)] (Figure 1A).Peripheral muscle ECV associated with CK (R2=0.307, rho=0.554, p=0.061) and was higher in SSc patients with evidence of myopathy compared to those with no myopathy [28 (10)% vs 15 (5)%, p=0.023] (Figure 1B). An ECV of 22% was determined to best identify myopathy with a sensitivity of 71% and a specificity of 80%.SSc patients had raised myocardial ECV and native T1 with means (SD) of 31 (3) % and 1287 (54) ms respectively (normal reference range ECV ≤29%, native T1 ≤1240ms). No clear association between myocardial and peripheral muscle ECV (rho=-0.485) or between myocardial ECV and peripheral muscle native T1 (rho=0.470) of SSc patients was observed.Conclusion:This pilot study to determine ECV-MRI of the peripheral muscle showed higher ECV in SSc patients compared to HV, suggesting the presence of diffuse fibrosis in the peripheral muscle of SSc patients. These data support further investigation to understand the pathophysiological involvement and relationship of peripheral and cardiac muscle in SSc.References:[1]Follansbee WP et al, Am Heart J. 1993[2]Barison A et al, Eur Heart J Cardiovasc Imaging. 2015Disclosure of Interests:Raluca-Bianca Dumitru: None declared, Alex Goodall: None declared, David Broadbent: None declared, Ananth Kidambi: None declared, Sven Plein: None declared, Francesco Del Galdo: None declared, Ai Lyn Tan: None declared, John Biglands: None declared, Maya H Buch Grant/research support from: Pfizer, Roche, and UCB, Consultant of: Pfizer; AbbVie; Eli Lilly; Gilead Sciences, Inc.; Merck-Serono; Sandoz; and Sanofi

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Outcomes and biomarker analyses among patients with COVID-19 treated with interleukin 6 (IL-6) receptor antagonist sarilumab at a single institution in Italy

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001089 ◽

2020 ◽

Vol 8 (2) ◽

pp. e001089 ◽

Cited By ~ 8

Author(s):

Vincenzo Montesarchio ◽

Roberto Parella ◽

Chiara Iommelli ◽

Antonella Bianco ◽

Elio Manzillo ◽

...

Keyword(s):

Receptor Antagonist ◽

Interleukin 6 ◽

Large Scale ◽

Elevated Serum ◽

Case Series ◽

Serum Levels ◽

Response To Treatment ◽

Single Institution ◽

Retrospective Case ◽

Potential Biomarker

BackgroundThe inflammatory pathology observed in severe COVID-19 disease caused by the 2019 novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by elevated serum levels of C reactive protein (CRP) and cytokines, including interferon gamma, interleukin 8 (IL-8), and interleukin 6 (IL-6). Initial reports from the outbreak in Italy, China and the USA have provided anecdotal evidence of improved outcomes with the administration of anti-IL-6 agents, and large-scale trials evaluating these therapies are ongoing.Study descriptionIn this retrospective case series, clinical outcomes and correlates of response to treatment with the IL-6 receptor antagonist sarilumab are described for 15 patients with COVID-19 from a single institution in Southern Italy. Among 10 patients whose symptoms improved after sarilumab treatment, rapid decreases in CRP levels corresponded with clinical improvement. Lower levels of IL-6 at baseline as well as lower neutrophil to lymphocyte ratio as compared with patients whose COVID-19 did not improve with treatment were associated with sarilumab-responsive disease.ConclusionsThis observation may reflect a possible clinical benefit regarding early intervention with IL-6-modulatory therapies for COVID-19 and that CRP could be a potential biomarker of response to treatment.

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Criteria positive and criteria negative anaphylaxis, with a focus on undifferentiated somatoform idiopathic anaphylaxis: A review and case series

Allergy and Asthma Proceedings ◽

10.2500/aap.2020.41.200076 ◽

2020 ◽

Vol 41 (6) ◽

pp. 436-441 ◽

Cited By ~ 1

Author(s):

Daniel A. Rosloff ◽

Kunal Patel ◽

Paul J. Feustel ◽

Jocelyn Celestin

Keyword(s):

Diagnostic Criteria ◽

Statistical Significance ◽

Case Series ◽

Poor Response ◽

Response To Treatment ◽

Fisher Exact Test ◽

Subjective Symptoms ◽

Significant Difference ◽

Physical Findings ◽

Idiopathic Anaphylaxis

Background: Undifferentiated somatoform (US) idiopathic anaphylaxis (IA) is considered a psychogenic disorder characterized by a lack of observable physical findings and poor response to treatment. Although failure to diagnose true anaphylaxis can have disastrous consequences, identification of US-IA is crucial to limit unnecessary expenses and use of health care resources. Objective: To better define the presentation and understand the potential relationship between US-IA and underlying psychiatric comorbidities. Methods: We retrospectively reviewed 110 visits by 107 patients to our institution for evaluation and management of anaphylaxis over a 1-year period. The patients were classified as having either criteria positive (CP) or criteria negative (CN) anaphylaxis based on whether they met Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network Symposium criteria for the clinical diagnosis of anaphylaxis. Patient characteristics, including objective and subjective signs and symptoms, and the presence of psychiatric diagnoses were collected and analyzed. Statistical significance was assessed by using the Fisher exact test. A literature review of US-IA and other psychogenic forms of anaphylaxis was performed. Results: Patients with CP anaphylaxis were more likely to present with hypotension, wheezing, urticaria, and vomiting than were patients with CN anaphylaxis. The patients with CN anaphylaxis were more likely to present with subjective symptoms of sensory throat tightness or swelling compared with patients with CP anaphylaxis. No significant difference was detected in the prevalence of psychiatric conditions between the two groups. Conclusion: Patients who met previously established diagnostic criteria for anaphylaxis were more likely to present with objective physical findings than those who did not meet criteria for true anaphylaxis. CN patients who presented for treatment of anaphylaxis were more likely to present with subjective symptoms. Formal diagnostic criteria should be used by clinicians when evaluating patients with suspected anaphylaxis.

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Melanoma: Prognostic Factors and Factors Predictive of Response to Therapy

Current Medicinal Chemistry ◽

10.2174/0929867326666191205160007 ◽

2020 ◽

Vol 27 (17) ◽

pp. 2792-2813

Author(s):

Martina Strudel ◽

Lucia Festino ◽

Vito Vanella ◽

Massimiliano Beretta ◽

Francesco M. Marincola ◽

...

Keyword(s):

Prognostic Factors ◽

Lactate Dehydrogenase ◽

Checkpoint Inhibitors ◽

Survival Rates ◽

Elevated Serum ◽

Predictive Biomarkers ◽

Response To Therapy ◽

Response To Treatment ◽

Prognostic Features ◽

Programmed Death

Background: A better understanding of prognostic factors and biomarkers that predict response to treatment is required in order to further improve survival rates in patients with melanoma. Predictive Biomarkers: The most important histopathological factors prognostic of worse outcomes in melanoma are sentinel lymph node involvement, increased tumor thickness, ulceration and higher mitotic rate. Poorer survival may also be related to several clinical factors, including male gender, older age, axial location of the melanoma, elevated serum levels of lactate dehydrogenase and S100B. Predictive Biomarkers: Several biomarkers have been investigated as being predictive of response to melanoma therapies. For anti-Programmed Death-1(PD-1)/Programmed Death-Ligand 1 (PD-L1) checkpoint inhibitors, PD-L1 tumor expression was initially proposed to have a predictive role in response to anti-PD-1/PD-L1 treatment. However, patients without PD-L1 expression also have a survival benefit with anti-PD-1/PD-L1 therapy, meaning it cannot be used alone to select patients for treatment, in order to affirm that it could be considered a correlative, but not a predictive marker. A range of other factors have shown an association with treatment outcomes and offer potential as predictive biomarkers for immunotherapy, including immune infiltration, chemokine signatures, and tumor mutational load. However, none of these have been clinically validated as a factor for patient selection. For combined targeted therapy (BRAF and MEK inhibition), lactate dehydrogenase level and tumor burden seem to have a role in patient outcomes. Conclusions: With increasing knowledge, the understanding of melanoma stage-specific prognostic features should further improve. Moreover, ongoing trials should provide increasing evidence on the best use of biomarkers to help select the most appropriate patients for tailored treatment with immunotherapies and targeted therapies.

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Reversal of DIRECT-ACTING Oral Anticoagulants in Urgent Surgery of the Proximal Aorta: case Series and Review of the literature

Current Pharmaceutical Design ◽

10.2174/1381612825666181226150006 ◽

2019 ◽

Vol 24 (38) ◽

pp. 4534-4539 ◽

Cited By ~ 1

Author(s):

Eric Zimmermann ◽

Fawzi Ameer ◽

Berhane Worku ◽

Dimitrios Avgerinos

Keyword(s):

Oral Anticoagulants ◽

Aortic Surgery ◽

Management Strategies ◽

Case Series ◽

Published Data ◽

Review Of Literature ◽

Clotting Factors ◽

Urgent Surgery ◽

Direct Acting ◽

Direct Acting Oral Anticoagulants

Introduction: Proximal aorta interventions impose significant bleeding risk. Patients on concomitant anticoagulation regimens compound the risk of bleeding in any surgery, but especially cardiothoracic interventions. The employment of direct-acting oral anticoagulants (DOAC), namely those that target clotting factors II or X, has expanded at a precipitous rate over the last decade. The emergence of their reversal agents has followed slowly, leaving clinicians with management dilemmas in urgent surgery. We discuss current reversal strategies based on the available published data and our experience with proximal aortic surgery in patients taking DOACs. Literature Search: We performed a review of literature and present three cases from our experience to offer insight into management strategies that have been historically successful. A review of literature was conducted via PubMed with the following search string: (NOAC or DOAC or TSOAC) and (aorta or aortic or (Stanford and type and a)). Case Presentation: We present three case presentations that illustrate the importance of DOAC identification and offer management strategies in mitigating associated bleeding risks in urgent or emergent surgeries. Conclusion: Treatment teams should be aware of the technical limitations of identifying and reversing DOACs. In view of the tendency toward publishing positive outcomes, more scientific rigor is required in the area of emergency DOAC reversal strategies.

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Neoplastic lesions in domestic pigs detected at slaughter: literature review and a 20-year review (1998–2018) of carcass inspection in Catalonia

Porcine Health Management ◽

10.1186/s40813-021-00207-0 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Antonia Morey-Matamalas ◽

Enric Vidal ◽

Jorge Martínez ◽

Jaume Alomar ◽

Antonio Ramis ◽

...

Keyword(s):

B Cell ◽

Case Series ◽

B Cell Lymphoma ◽

Support Network ◽

Published Data ◽

Nerve Sheath Tumor ◽

Lymphoid Leukemia ◽

Lymphoid Neoplasms ◽

Neoplastic Lesions ◽

Slaughtered Pigs

Abstract Background The present paper reviews the occurrence of neoplasms in swine and presents a case series of 56 tumors submitted to the Slaughterhouse Support Network (Servei de Suport a Escorxadors [SESC] IRTA-CReSA]) from slaughtered pigs from 1998 to 2018 (April) in Catalonia (Spain). The aim of the study was to describe the spectrum of spontaneous neoplastic lesions found in slaughtered pigs and to compare the reported tumor cases with previous published data. Lymphoid neoplasms were characterized and classified using the WHO classification adapted for animals. Results The most reported neoplasm during this period was lymphoma (28). Within lymphomas, the B-cell type was the most common, being the diffuse large B-cell lymphoma (15/28) the most represented subtype. Other submitted non-lymphoid neoplasms included melanoma (7), nephroblastoma (3), mast cell tumor (2), liposarcoma (2), osteochondromatosis (2), papillary cystadenocarcinoma (1), peripheral nerve sheath tumor (1), lymphoid leukemia (1), fibropapilloma (1), hemangiosarcoma (1), hepatoma (1), histiocytic sarcoma (1), pheochromocytoma (1) and osteosarcoma (1). Conclusions The existence of a well-established Slaughterhouse Support Network allowed the compilation of comprehensive data for further epidemiological and pathological studies, particularly about less commonly reported lesions in livestock such as neoplasms in pigs.

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Post-Infectious Guillain–Barré Syndrome Related to SARS-CoV-2 Infection: A Systematic Review

Life ◽

10.3390/life11020167 ◽

2021 ◽

Vol 11 (2) ◽

pp. 167

Author(s):

Pasquale Sansone ◽

Luca Gregorio Giaccari ◽

Caterina Aurilio ◽

Francesco Coppolino ◽

Valentina Esposito ◽

...

Keyword(s):

Single Case ◽

Case Reports ◽

Case Series ◽

Guillain Barre Syndrome ◽

Response To Treatment ◽

Comprehensive Overview ◽

Fisher Syndrome ◽

Immunomodulating Therapy ◽

Guillain Barré Syndrome ◽

Guillain Barré

Background. Guillain-Barré syndrome (GBS) is the most common cause of flaccid paralysis, with about 100,000 people developing the disorder every year worldwide. Recently, the incidence of GBS has increased during the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) epidemics. We reviewed the literature to give a comprehensive overview of the demographic characteristics, clinical features, diagnostic investigations, and outcome of SARS-CoV-2-related GBS patients. Methods. Embase, MEDLINE, Google Scholar, and Cochrane Central Trials Register were systematically searched on 24 September 2020 for studies reporting on GBS secondary to COVID-19. Results. We identified 63 articles; we included 32 studies in our review. A total of 41 GBS cases with a confirmed or probable COVID-19 infection were reported: 26 of them were single case reports and 6 case series. Published studies on SARS-CoV-2-related GBS typically report a classic sensorimotor type of GBS often with a demyelinating electrophysiological subtype. Miller Fisher syndrome was reported in a quarter of the cases. In 78.1% of the cases, the response to immunomodulating therapy is favourable. The disease course is frequently severe and about one-third of the patients with SARS-CoV-2-associated GBS requires mechanical ventilation and Intensive Care Unit (ICU) admission. Rarely the outcome is poor or even fatal (10.8% of the cases). Conclusion. Clinical presentation, course, response to treatment, and outcome are similar in SARS-CoV-2-associated GBS and GBS due to other triggers.

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Characteristics and Outcomes Among Hospitalized COVID-19-Positive Patients in a Nonurban Environment

Military Medicine ◽

10.1093/milmed/usab044 ◽

2021 ◽

Author(s):

Robert P Lennon ◽

Theodore J Demetriou ◽

M Fahad Khalid ◽

Lauren Jodi Van Scoy ◽

Erin L Miller ◽

...

Keyword(s):

New York ◽

Medical Center ◽

Academic Medical Center ◽

Military Medicine ◽

Case Series ◽

Outcome Data ◽

Urban Environments ◽

Urban Setting ◽

Published Data ◽

Retrospective Case

ABSTRACT Introduction Virtually all hospitalized coronavirus disease-2019 (COVID-19) outcome data come from urban environments. The extent to which these findings are generalizable to other settings is unknown. Coronavirus disease-2019 data from large, urban settings may be particularly difficult to apply in military medicine, where practice environments are often semi-urban, rural, or austere. The purpose of this study is compare presenting characteristics and outcomes of U.S. patients with COVID-19 in a nonurban setting to similar patients in an urban setting. Materials and Methods This is a retrospective case series of adults with laboratory-confirmed COVID-19 infection who were admitted to Hershey Medical Center (HMC), a 548-bed tertiary academic medical center in central Pennsylvania serving semi-urban and rural populations, from March 23, 2020, to April 20, 2020 (the first month of COVID-19 admissions at HMC). Patients and outcomes of this cohort were compared to published data on a cohort of similar patients from the New York City (NYC) area. Results The cohorts had similar age, gender, comorbidities, need for intensive care or mechanical ventilation, and most vital sign and laboratory studies. The NYC’s cohort had shorter hospital stays (4.1 versus 7.2 days, P < .001) but more African American patients (23% versus 12%, P = .02) and higher prevalence of abnormal alanine (>60U/L; 39.0% versus 5.9%, P < .001) and aspartate (>40U/L; 58.4% versus 42.4%, P = .012) aminotransferase, oxygen saturation <90% (20.4% versus 7.2%, P = .004), and mortality (21% versus 1.4%, P < .001). Conclusions Hospitalists in nonurban environments would be prudent to use caution when considering the generalizability of results from dissimilar regions. Further investigation is needed to explore the possibility of reproducible causative systemic elements that may help improve COVID-19-related outcomes. Broader reports of these relationships across many settings will offer military medical planners greater ability to consider outcomes most relevant to their unique settings when considering COVID-19 planning.

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THU0351 MUSCLE INVOLVEMENT IN PATIENTS WITH SYSTEMIC SCLEROSIS AND ANTI-PM/SCL+ ANTIBODIES IS ASSOCIATED WITH CARDIAC AND PULMONARY INVOLVEMENT. ANALYSIS OF THE MULTICENTRE EUSTAR COHORT.

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3525 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 407.1-407

Author(s):

M. G. Lazzaroni ◽

S. Zingarelli ◽

P. Airò ◽

Y. Allanore ◽

O. Distler

Keyword(s):

Systemic Sclerosis ◽

Cardiac Involvement ◽

Severe Disease ◽

Disease Onset ◽

Pulmonary Involvement ◽

Left Ventricular ◽

Research Support ◽

Muscle Involvement ◽

Group A ◽

Tendon Friction Rubs

Background:Anti-PM/Scl antibodies positivity has been associated with frequent skeletal muscle involvement in patients with Systemic Sclerosis (SSc) in different studies, including the EUSTAR cohort (1). Moreover, although myositis has been previously associated with heart involvement in SSc patients (2), this issue has never been explored among anti-PM/Scl+ patients.Objectives:To evaluate the cardiac involvement in anti-PM/Scl patients with SSc in the large multicentre EUSTAR database, with focus on the subgroup of patients with muscle involvement.Methods:Patients from the EUSTAR database were included when the item anti-PM/Scl was fulfilled in at least one visit.Results:Anti-PM/Scl status was available in 7,353 SSc patients from EUSTAR database: 295 were anti-PM/Scl+. After exclusion of 151 patients with multiple autoantibody positivity, 144 anti-PM/Scl + patients were compared with 7,058 anti-PM/Scl- patients. Among them, 3,120 (44.2%) were positive for ACA, 2,361 (33.5%) for anti-Topo I and 274 (3.88%) for anti-RNAP3.Regarding the specific cardiac outcomes, in the anti-PM/Scl+ as compared to the anti-PM/Scl- group, a decreased rate of elevated sPAP at ECHO was recorded (12.8% vs 25.0%, p:0.001), while no differences were observed in the frequency of conduction blocks (26.2% vs 23.7%, p:0.526), abnormal diastolic function (33.9% vs 36.4%, p:0.582), pericardial effusion (10.2% vs 10.9%, p:1.000) and LVEF ≤50% (4.76% vs 6.11%, p:0.818). In multivariate analysis, adjusted for age at disease onset, sex, and disease duration, the negative association of anti-PM/Scl with elevated sPAP was not confirmed (p:0.061).When comparing anti-PM/Scl+ patients with (n=47) and without (n=87) CK elevation, the former group had a higher frequency of conduction blocks (43.2% vs 17.5%, p:0.005; OR 95% CI 3.47, 1.51-7.97) and left ventricular dysfunction, both diastolic (45.6% vs 27.2%, p:0.050; OR 95% CI 2.25, 1.05-4.81) and systolic (LVEF ≤50% 13.3% vs 0%, p:0.018; OR 95% CI 16.8, 0.87-324). Moreover, anti-PM/Scl+ patients with CK elevation had significantly increased rate of lung fibrosis on HRCT (p:0.045), intestinal symptoms (p:0.017), joint contractures (p:0.045) and tendon friction rubs (p:0.034).Conclusion:In the largest series of anti-PM/Scl positive SSc patients so far reported, muscle involvement in anti-PM/Scl+ patients (defined as increased serum CK) seems to represent a marker of a more severe disease phenotype, including a higher frequency of cardio-pulmonary involvement.References:[1]Lazzaroni MG, et al. Ann Rheum Dis 2018. 77 (2), 421-2.[2]Follansbee WP, et al. Am Heart J 1993. 125: 194-203.Acknowledgments:Authors would like to thank the patients’ association GILS (Gruppo Italiano Lotta Sclerodermia) for the grant that supported the project.Disclosure of Interests:Maria Grazia Lazzaroni: None declared, Stefania Zingarelli: None declared, Paolo Airò: None declared, Yannick Allanore Grant/research support from: BMS, Inventiva, Roche, Sanofi, Consultant of: Actelion, Bayer AG, BMS, BI, Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche

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