Anti-Synthetase Syndrome Complicated by Pyogenic Myositis

Background: Anti-synthetase syndrome is a rare autoimmune disorder characterized by autoantibodies against aminoacyl-tRNA-synthetases. Inflammatory myopathy and interstitial lung disease could be present among other manifestations. Anti-Jo-1 is the most common antisynthetase antibody and is the most likely to present with the classic triad (interstitial lung disease, myositis, and arthritis) and have more muscle and joint involvement than patients with other antisynthetase antibodies. Case report: Here, we present a case of a 60-year-old female patient, with a previous diagnosis of myositis, secondary to the anti-synthetase syndrome, with a complication by pyogenic myositis. Conclusion: Diagnosis is made by a multidisciplinary approach, occasionally muscle and/or lung biopsy are needed. Imaging studies, Especially magnetic resonance imaging, based on findings such as muscle and fascial edema, and fatty tissue replacement, allow an optimal approach.

SINDROME ANTISINTETASA EN TIEMPO DE PANDEMIA

Introduction Introduction: The Antisynthetase Syndrome is a rare entity that is included within the idiopathic inflammatory myopathies, characterized by the presence of antisynthetase antibodies, they can be found in 39.1% of the patients with these myopathies. The affectation is systemic being the main ones at the articular level in 40% -80%. Lung damage occurs in 60% -80%, the most frequent findings being ground glass, predominantly crosslinking in lower segments, probably with a pattern of non-specific interstitial pneumonia, organized pneumonia, or mixed patterns. Regarding muscle involvement, it occurs in 60% -80%. Treatment is based on the use of corticosteroids, immunosuppressants, and biological agents. Case description A 38-year-old female patient with no significant clinical or family history was approached, single (no children), who presented gradual and intermittent joint pain and muscle weakness associated with progressive dyspnea, in the context of The current pandemic was swabbed for SARS-COV-2 on two occasions as well as antibodies for the same virus being negative, with tomographic findings compatible with an alternative pattern, despite the aforementioned, it was treated in a particular way with a scheme directed towards COVID -19, with partial resolution of the symptoms and subsequent exacerbation of the same, for which he went to hospital care, where the swab was repeated obtaining negativity of the same, deciding on this occasion an evaluation by the Pneumology Service and hospitalization. During his stay, an immunological panel was performed where a weak elevation of rheumatoid factor is evidenced, due to logistical issues Myositis panel we are waiting, however, due to the lack of specific etiology, it was decided to perform a lung biopsy reporting a concordant pattern of organized pneumonia With the tomographic diagnosis, the evolution of the patient was favorable with supportive treatment until the results of the external immunological panel were received, evidencing a marked elevation of the anti-Jo antibody, added to the clinical and image manifestations, the picture is cataloged as an Antisynthetase Syndrome. Thus, with the support of rheumatology, treatment with corticosteroids (methylprednisolone), immunosuppressants (mycophenolate) and biological agent (rituximab) is started; with which there was significant clinical improvement, decrease in o2 support as well as lung lesions, with which we proceeded to discharge with the respective follow-up by the services involved. Conclusions: As we evidenced in the clinical case, in a retrospective way, we can assert that it complied with the clinical manifestations of the disease, although we are experiencing a pandemic where lung involvement is important, once it has been ruled out, other diagnostic possibilities must be addressed. As in the patient, it culminated in the presentation of a rheumatological picture with lung damage.

AB0092 ANTISYNTHETASE SYNDROME: CLINICAL PROFILE, SEROLOGIC AND TREATMENTS USED IN A COHORT OF PATIENTS FOLLOWED AT THE VIRGEN MACARENA HOSPITAL

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

POS1229 ANTI-MDA5 AND ANTISYNTHETASE ANTIBODIES SCREENING IN SEVERE SARS-COV-2 PNEUMONIA. BE AWARE OF FALSE POSITIVE RESULTS

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

Case of late diagnosis of dermatomyositis with anti-synthetic syndrome

Полимиозит (ПМ) и дерматомиозит (ДМ) — аутоиммунные заболевания скелетной мускулатуры неизвестной этиологии, которые относятся к системным заболеваниям соединительной ткани и объединяются общим термином «идиопатические воспалительные миопатии». Наиболее тяжелым подтипом полимиозита и дерматомиозита (ПМ/ДМ) является антисинтетазный синдром (АСС), ассоциированный с наличием специфических иммунологических маркеров в сыворотке крови – антисинтетазных антител. АСС имеет клинические особенности, отличающие его от группы ПМ/ДМ в целом. Интерстициальное заболевание легких – наиболее распространенное экстрамускулярное поражение при ПМ/ДМ является ключевым прогностическим фактором течения заболевания, а также определяет терапевтическую тактику и прогноз. Трудности своевременной диагностики ДМ с АСС зачастую связаны с тем, что заболевание может начинаться с легочной симптоматики при отсутствии явных признаков миопатии. Представлен клинический случай поздней диагностики данного заболевания. Polymyositis (PM) and dermatomyositis (DM) are autoimmune diseases of skeletal muscles of unknown etiology, which belong to systemic diseases of the connective tissue and are collectively called «idiopathic inflammatory myopathies». The most severe subtype of polymyositis and dermatomyositis (PM/DM) is antisynthetase syndrome (ACC), associated with the presence of specific immunological markers in the blood serum – antisynthetase antibodies. ACC has clinical features that distinguish it from the PM/DM group as a whole. Interstitial lung disease, the most common extramuscular lesion in PM/DM, is a klyuchevoy prognostic factor in the course of the disease, as well as determining therapeutic tactics and prognosis. Difficulties in the timely diagnosis of DM with ACC are often associated with the fact that the disease can begin with pulmonary symptoms in the absence of obvious signs of myopathy. A clinical case of late diagnosis of this disease is presented.

Role of autoantibodies in the diagnosis and prognosis of interstitial lung disease in autoimmune rheumatic disorders

Interstitial lung disease (ILD) has been recognized as a frequent manifestation associated with a substantial morbidity and mortality burden in patients with autoimmune rheumatic disorders. Serum autoantibodies are considered good biomarkers for identifying several subsets or specific phenotypes of ILD involvement in these patients. This review features the role of several autoantibodies as a diagnostic and prognostic biomarker linked to the presence ILD and specific ILD phenotypes in autoimmune rheumatic disorders. The case of the diverse antisynthetase antibodies in the antisynthease syndrome or the anti-melanoma differentiation-associated 5 protein (MDA5) antibodies as a marker of a severe condition such as rapidly progressive ILD in patients with clinically amyopathic dermatomyositis are some of the associations herein reported in the group of myositis spectrum disorders. Specific autoantibodies such as the well-known anti-topoisomerase I (anti-Scl70) or the anti-Th/To, anti-U11/U12 ribonucleoprotein, and anti-eukaryotic initiation factor 2B (eIF2B) antibodies seems to be specifically linked to ILD in patients with systemic sclerosis. Overlap syndromes between systemic sclerosis and myositis, also have good ILD biomarkers, which are the anti-PM/Scl and anti-Ku autoantibodies. Lastly, other not so often reported disorders as being associated with ILD but recently most recognized as is the case of rheumatoid arthritis associated ILD or entities herein included in the miscellaneous disorders section, which include anti-neutrophil cytoplasmic antibody-associated interstitial lung disease, Sjögren’s syndrome or the mixed connective tissue disease, are also discussed.

Functional Progression in Patients with Interstitial Lung Disease Resulted Positive to Antisynthetase Antibodies: A Multicenter, Retrospective Analysis

Antisynthetase syndrome (ASSD) is a rare autoimmune disease characterized by serologic positivity for antisynthetase antibodies. Anti-Jo1 is the most frequent, followed by anti PL-7, anti PL-12, anti EJ, and anti OJ antibodies. The lung is the most frequently affected organ, usually manifesting with an interstitial lung disease (ILD), which is considered the main determinant of prognosis. Some evidences suggest that non-anti-Jo-1 antibodies may be associated with more severe lung involvement and possibly with poorer outcomes, while other authors do not highlight differences between anti-Jo1 and other antisynthetase antibodies. In a multicenter, retrospective, “real life” study, we compared lung function tests (LFTs) progression in patients with ILD associated with anti-Jo1 and non-anti-Jo1 anti-synthetase antibodies to assess differences in lung function decline between these two groups. Therefore, we analyzed a population of 57 patients (56% anti-Jo1 positive), referred to the outpatient Clinic of four referral Centers in Italy (Modena, Monza, Siena, and Trieste) from 2008 to 2019, with a median follow-up of 36 months. At diagnosis, patients showed a mild ventilatory impairment and experienced an improvement of respiratory function during treatment. We did not observe statistically significant differences in LFTs at baseline or during follow-up between the two groups. Moreover, there were no differences in demographic data, respiratory symptoms onset (acute vs. chronic), extrapulmonary involvement, treatment (steroid and/or another immunosuppressant), or oxygen supplementation. Our study highlights the absence of differences in pulmonary functional progression between patients positive to anti-Jo-1 vs. non anti-Jo-1 antibodies, suggesting that the type of autoantibody detected in the framework of ASSD does not affect lung function decline.

Influence of Antisynthetase Antibodies Specificities on Antisynthetase Syndrome Clinical Spectrum Time Course

Antisynthetase syndrome (ASSD) is a rare clinical condition that is characterized by the occurrence of a classic clinical triad, encompassing myositis, arthritis, and interstitial lung disease (ILD), along with specific autoantibodies that are addressed to different aminoacyl tRNA synthetases (ARS). Until now, it has been unknown whether the presence of a different ARS might affect the clinical presentation, evolution, and outcome of ASSD. In this study, we retrospectively recorded the time of onset, characteristics, clustering of triad findings, and survival of 828 ASSD patients (593 anti-Jo1, 95 anti-PL7, 84 anti-PL12, 38 anti-EJ, and 18 anti-OJ), referring to AENEAS (American and European NEtwork of Antisynthetase Syndrome) collaborative group’s cohort. Comparisons were performed first between all ARS cases and then, in the case of significance, while using anti-Jo1 positive patients as the reference group. The characteristics of triad findings were similar and the onset mainly began with a single triad finding in all groups despite some differences in overall prevalence. The “ex-novo” occurrence of triad findings was only reduced in the anti-PL12-positive cohort, however, it occurred in a clinically relevant percentage of patients (30%). Moreover, survival was not influenced by the underlying anti-aminoacyl tRNA synthetase antibodies’ positivity, which confirmed that antisynthetase syndrome is a heterogeneous condition and that antibody specificity only partially influences the clinical presentation and evolution of this condition.