High frequency of muscle activity relapses in anti-synthetase syndrome

High frequency of muscle activity relapses in anti-synthetase syndrome | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article High frequency of muscle activity relapses in anti-synthetase syndrome Kaioan Choma, Caio Gabriel Jeronymo Lima Brasileiro, Fernando Henrique Carlos De Souza, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5876556/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background To date, no study has analyzed muscular activity relapses in anti-synthetase syndrome (ASyS), underscoring the necessity for this investigation. Methods . This single-center retrospective cohort study, conducted between 2010 and 2014, included patients with anti-Jo-1 ASyS. Results . A total of 95 patients with ASyS were identified. However, we excluded patients with anti-aminoacyl-tRNA-synthetase non-Jo-1 antibodies (n = 26), or myositis-associated autoantibodies (n = 25), without muscle involvement (n = 10), and those with incomplete data (n = 2). Consequently, a total of 48 anti-Jo-1 ASyS patients were evaluated with a median age of 44 (interquartile range: 35–54) years, predominantly female (81.3%), and of white ethnicity (79.2%). The median follow-up period was 80 (26–126) months. Twenty patients (41.7%) experienced second muscle activity during follow-up, whereas 10 (20.8%) and four (10.4%) experienced third and fourth muscle relapses, respectively. Compared to those without muscle relapse (n = 20), patients with at least one muscle relapse (n = 28) were younger (48 vs . 39 years, respectively; P = 0.020), exhibited a higher median creatine phosphokinase level (4144 vs . 8124U/L; P = 0.019), and demonstrated lower rates of pulmonary involvement, specifically ground-glass opacity (P = 0.006) and lung fibrosis (P = 0.003). There was no significant difference in treatment between patients with and without muscle relapse, except for cyclophosphamide, which was more frequently utilized in patients without muscle relapse (5.0% vs . 32.9%; P = 0.031). Conclusion . A high frequency of muscle activity relapse was observed in patients with ASyS, particularly among younger individuals with high initial creatine phosphokinase levels and reduced pulmonary involvement. A small subset of patients experienced more than three muscle relapses. Anti-synthetase syndrome inflammatory myopathy myositis prognosis relapse INTRODUCTION Anti-synthetase syndrome (ASyS) is classified within the group of systemic autoimmune myopathies and is characterized by the presence of antibodies against aminoacyl-tRNA synthetase (anti-ARS), with anti-Jo-1 being the most prevalent [ 1 ]. The primary clinical manifestations include myositis, arthritis, interstitial lung disease (ILD), fever, mechanic’s hands, and Raynaud’s phenomenon [ 2 – 4 ]. The clinical phenotype of ASyS is associated with specific antibody present, as demonstrated in the scientific literature [ 4 ]. For instance, anti-Jo-1 patients exhibit a higher incidence of myositis, polyarthritis and ILD, whereas anti-PL-12 and anti-PL-7 patients present with a higher incidence of isolated ILD, in addition to increased mortality [ 5 , 6 ]. Studies on ASyS remain limited owing to the rarity of the disease, particularly regarding the description of muscle activity relapses. Retrospective cohorts frequently emphasize joint and lung manifestations due to their diagnostic challenges and the significant impact of ILD on patient survival [ 6 , 7 ]. However, there has been insufficient characterization of the behavior of muscle manifestations during patient follow-up. Therefore, this study aimed to evaluate the frequency of muscle activity relapse in adult patients with anti-Jo-1 ASyS. Second, to it sought to describe factors associated with these relapses. PATIENTS AND METHODS Study design. This single-center retrospective cohort study included adult patients with anti-Jo-1 ASyS under regular follow-up at our rheumatology tertiary outpatient clinic between January 2010 and March 2014. The study was approved by the local ethics committee (CAAE 93514918.0.0000.0068). Inclusion criteria. We included adult patients with at least two of the three disorders: joint, lung, and/or muscle involvement. Additionally, the presence of persistent fever, Raynaud’s phenomenon and/or “mechanic’s hands” was considered [ 3 ]. However, the presence of muscle involvement was mandatory and, as anti-ARS, only anti-Jo-1 autoantibodies were considered in the present study. Exclusion criteria. Patients with incomplete data, patients with overlap syndrome or cancer-associated myositis were excluded. Patients’ data. The following pre-standardized and pre-parameterized data were collected from the patients' electronic records: Demographic data: age at ASyS’s diagnosis, ethnicity, and sex; Clinical and laboratory data: disease duration, occurrence of muscle flares, laboratory data, and clinical manifestations at disease onset); the identification of the anti-synthetase autoantibodies [anti-Jo-1, anti-PL-7, anti-PL-12, anti-OJ, and anti-EJ] were determined by a commercially available line blot test kit (Myositis Profile Euroline Blot test kit, Euroimmun, Lübeck, German). Assessment was performed according to a previously established method [ 8 ]; muscle involvement and activity were defined as the presence of objective limb muscle weakness - scores of the Medical Research Council - MRC [ 9 ], elevated serum levels - at least twice the upper limit - creatine phosphokinase (CPK, reference value: 26–192 U/L), alanine aminotransferase (ALT, < 31 U/L), aspartate aminotransferase (AST, < 31 U/L), and lactic dehydrogenase (LDH, 135–214 U/L). Thigh muscle magnetic resonance imaging with identification of muscle edema was also included when available. Myopathic patterns on electroneuromyography and muscle biopsy compatible with inflammatory myopathy were also considered to define muscle involvement. Lung involvement was based on the presence of dyspnea and signs suggestive of pulmonary involvement secondary to ASyS on high-resolution computed tomography (CT) of the chest performed at the initial follow-up. The presence or absence of interstitial lung, ground-glass opacity, or lung fibrosis were considered; joint involvement was defined as nonerosive and nondeforming arthritis; treatment (glucocorticoids, immunosuppressive, immunomodulatory, and immunobiological drugs). Statistical analysis was conducted. The Shapiro-Wilk test was employed to assess the distribution of each parameter. The results were presented as median (interquartile range: 25th − 75th ) for continuous variables, whereas categorical variables were presented as frequency (%). Results were compared using t-Student or Mann-Whitney tests for continuous variables to determine differences between patients with ASyS and the presence or absence of the first muscle disease relapse. Differences in categorical variables were calculated using Fisher’s exact test and Pearson’s χ 2 test. Differences were considered statistically significant at P < 0.05. Statistical analyses were performed using the SPSS software (version 15.0, Chicago, IL, USA). RESULTS A total of 95 adult patients diagnosed with ASyS were identified and followed up at our service. Twenty-six patients with non-Jo-1 anti-ARS antibodies or the presence of myositis-associated autoantibodies were excluded. Of the remaining 69 patients, 10 were excluded due to the absence of muscle involvement, and another two were excluded for incomplete data. Thus, the final analysis included 48 adult patients with anti-Jo-1 ASyS. The patients had a median age of 44 (35–57) years, with a predominance of females (81.2%) and individuals of white ethnicity (79.2%). The mean total follow-up time was 80 (26–126) months. Among the 48 patients, 20 experienced new muscle activity (relapse group). Table 1 summarizes the general and initial data of the patients, categorized by the presence (n = 20) or absence (n = 28) of muscle relapse. Patients with muscle relapses were younger at the time of diagnosis compared to the non-relapse group (P = 0.020), with no significant differences observed in terms of sex or ethnicity. Table 1 General and initial feature comparison between ASyS anti-Jo-1 patients with presence or absence of muscle relapse Muscle relapse (N = 20) No muscle relapse (N = 28) P value Age at disease onset (years) 39 (28–50) 48 (40–57) 0.020 Female sex 19 (95.0) 20 (71.4) 0.061 White ethnicity 15 (75.0) 23 (82.1) 0.721 Diagnosis - symptom’s onset (mo) 11 (3–7) 19 (2–13) 0.983 Initial disease manifestation Muscle involvement 20 (100) 28 (100) > 0.999 Upper limb strength Grade V 0 1 (3.6) 0.627 Grade IV 14 (70.0) 20 (71.4) Grade III 5 (25.0) 5 (17.9) Grade II 1 (5.0) 2 (7.1) Lower limb strength Grade V 1 (5.0) 2 (7.1) 0.707 Grade IV 13 (65.0) 19 (67.9) Grade III 5 (25.0) 5 (17.9) Grade II 1 (5.0) 2 (7.1) Laboratory data CPK (U/L) 8124 (2746–13803) 4144 (636–5975) 0.019 AST (U/L) 469 (88–461) 228 (43–246) 0.093 ALT (U/L) 210 (94–332) 252 (39–169) 0.066 LDH (U/L) 1180 (649–1511) 969 (350–1219) 0.165 Joint involvement 13 (65.0) 23 (82.1) 0.721 Lung involvement 17 (85.0) 24 (85.7) > 0.999 Dyspneae 16 (80.0) 24 (85.7) 0.703 Computed tomography Interstitial lung 17 (85.0) 23 (82.1) > 0.999 Ground-glass opacity 3 (15.0) 16 (57.1) 0.006 Lung fibrosis 0 10 (35.7) 0.003 Raynaud phenomenon 14 (70.0) 16 (57.1) 0.546 Fever 14 (70.0) 16 (57.1) 0.546 Mechanic’s hands 13 (65.0) 17 (60.7) > 0.999 Treatment Pulse therapy with MP 13 (65.0) 6 (30.0) 0.154 IVIG 12 (42.9) 7 (25.0) 0.750 Oral glucocorticoid 20 (100) 28 (100) > 0.999 Azathioprine 12 (60.0) 16 (57.1) > 0.999 Methotrexate 8 (40.0) 7 (25.0) 0.349 Cyclophosphamide IV 1 (5.0) 9 (32.9) 0.031 Cyclosporine 1 (5.0) 0 0.417 Mycophenolate mofetil 3 (15.0) 1 (3.6) > 0.999 Data are expressed as median (25th – 75th ), or frequency (%). ALT: alanine aminotransferase; ASyS: anti-synthetase syndrome; AST: aspartate aminotransferase; CPK: creatine phosphokinase; LDH: lactic dehydrogenase; IV: intravenous; IVIG: immunoglobulin; mo: month. Regarding the initial clinical manifestations, there were no differences between the groups, nor in the degree of muscle involvement according to the MRC scale. However, a statistically significant difference was found in the initial CPK levels, which were nearly twice as high in the muscle relapse group (P = 0.019). The presence of joint disease, ILD, Raynaud’s phenomenon, and mechanic’s hands was similar between the groups. However, lung involvement, as assessed by chest CT, demonstrated fewer interstitial or fibrotic changes in the non-relapse group (P = 0.006). Regarding treatment, both groups received similar therapies, including corticosteroid therapy and oral immunosuppressants. However, the non-relapse group exhibited a higher frequency of intravenous cyclophosphamide use. Table 2 provides the follow-up data for patients with muscle relapse (n = 20), stratified by the number of relapses: single, double, or three or more episodes. This includes clinical and laboratory characterizations of the episodes. Table 2 Follow up of 20 ASyS anti-Jo-1 patients with presence of muscle relapse 1st muscle relapse (N = 20) 2nd muscle relapse (N = 10) 3rd muscle relapse (N = 4) ASyS diagnosis - symptoms (mo) 12 (15–38) 28 (15–73) 44 (36–94) Upper limb strength Grade V 7 (35.0) 7 (70.0) 0 Grade IV 10 (50.0) 2 (20.0) 4 (100) Grade III 3 (15.0) 0 0 Grade II 0 1 (10.0) 0 Lower limb strength Grade V 3 (15.0) 2 (20.0) 0 Grade IV 16 (80.0) 7 (70.0) 3 (75.0) Grade III 1 (5.0) 0 1 (25.0) Grade II 0 1 (10.0) 0 Laboratory data CPK (U/L) 200 (1244–5278) 2832 (1836–4488) 3294 (155–5882) AST (U/L) 66 (43–190) 105 (69–173) 95 (76–234) ALT (U/L) 48 (38–137) 93 (47–140) 60 (49–136) LDH (U/L) 494 (350–761) 594 (430–851) 480 (339–1202) Other disease features Joint activity 3 (15.0) 2 (20.0) 3 (75.0) Lung activity 7 (35.0) 2 (20.0) 1 (25.0) Treatment before new mm symptoms Oral glucocorticoid 10 (50.0) 6 (60.0) 1 (25.0) Median dose (mg/day) 13 (9–33) 30 (20–45) 20 Azathioprine 8 (40.0) 2 (20.0) 2 (50.0) Methotrexate 7 (35.0) 4 (40.0) 2 (50.0) Cyclophosphamide IV 0 0 0 Cyclosporine 0 1 (10.0) 0 Mycophenolate mofetil 5 (25.0) 2 (20.0) 0 Leflunomide 1 (5.0) 2 (20.0) 0 Treatment after new mm symptoms Pulse therapy with MP 13 (65.0) 6 (60.0) 1 (25.0) IVIG 6 (30.0) 4 (40.0) 1 (25.0) Oral glucocorticoid 20 (100) 4 (100) Azathioprine 3 (15.0) 2 (20.0) Methotrexate 5 (25.0) 1 (10.0) 1 (25.0) Cyclophosphamide IV 1 (5.0) Cyclosporine 1 (5.0) 1 (10.0) 2 (50.0) Mycophenolate mofetil 5 (25.0) Leflunomide 2 (10.0) Rituximab 8 (40.0) 3 (30.0) 4 (100) Data are expressed as median (25th – 75th ), or frequency (%). ALT: alanine aminotransferase; ASyS: anti-synthetase syndrome; AST: aspartate aminotransferase; CPK: creatine phosphokinase; LDH: lactic dehydrogenase; IV: intravenous; IVIG: immunoglobulin; mm: muscle; mo: month. Among the 20 patients, 10 experienced a second relapse, and four experienced a third episode of muscular activity. Patients with new relapses demonstrated mean CPK levels 14–16 times above the reference value. Prior to the first muscular episode, only 10 of the 20 patients (50.0%) were receiving oral corticosteroid therapy, with a mean prednisone dose of 13 mg/day in the single-relapse group and 30 mg /day in the multiple-relapse group. The most frequently utilized corticosteroid-sparing immunosuppressants were methotrexate, azathioprine, and mycophenolate mofetil. Following the first episode of muscular activity, 13 patients (65.0%) received pulse therapy with methylprednisolone, and six (30.0%) were treated with intravenous human immunoglobulin (IVIg). In subsequent relapse episodes, the utilization of IVIg and rituximab increased. DISCUSSION This study demonstrated that younger anti-Jo-1 ASyS patients, with elevated initial CPK levels and without ground-glass opacities or pulmonary fibrosis on chest CT, are associated with increased muscle activity relapse. Given that the clinical presentation phenotype of ASyS varies according to the specific associated antibody [ 4 – 6 ], this study included only anti-Jo-1-positive patients to enhance sample homogeneity and mitigate confounding factors. Furthermore, anti-Jo-1 was selected due to its higher frequency in ASyS and its association with a higher incidence of myositis compared to non-anti-Jo-1 patients. The presence of myopathy is one of the cardinal symptoms of ASyS, characterized by elevated muscle enzymes along with muscle biopsy, muscle magnetic resonance imaging, or electromyography evidence of myositis [ 10 ]. Although myositis may not be present at disease onset, it develops in the majority of ASyS patients over the course of the disease [ 7 ]. The largest cohort described to date of ASyS patients reported a 55.1% prevalence of myositis in anti-Jo1 patients at disease onset, which increased to 82.1% after 72 months of follow-up, with 20% presenting the hypomyopathic form [ 7 ]. Similarly, the Euromyositis registry demonstrated that 90% of anti-ARS-positive ASyS patients exhibited myopathy with muscle weakness [ 11 ]. This study included only patients with the classic form of myositis, ensuring greater precision in assessing muscle relapses, facilitating relapse measurement, and focusing on the most impactful muscular outcome on patients' quality of life: muscle weakness. There are limited studies evaluating muscle relapse in ASyS. Marie et al. [ 12 ]. assessed the characteristics of anti-Jo1 ASyS patients with and without the presence of anti-Ro-52, reporting a muscle recurrence rate of 63.9% in 36 patients from the anti-Ro-52-positive group after a median follow-up period of 33.5 months. The number of relapses ranged from 0 to 3, and 78.3% occurred shortly after therapy tapering. These findings were not statistically significant when compared to the anti-Ro-52-negative group (53 patients). This investigation did not evaluate the factors associated with muscle relapse. A Japanese cohort evaluated 40 ASyS patients with six different anti-ARS antibodies over an average follow-up period of 39.6 months. Of these, 26 patients (65%) responded to immunosuppressive therapy, demonstrating improved muscle strength and reduced CPK levels. However, muscle relapse was observed in seven patients (26.9%), of whom only one was positive for the anti-Jo-1 antibody [ 13 ]. Our study identified a high rate of muscle relapse (42% of patients), particularly in younger patients at diagnosis, those with markedly elevated CPK levels at initial presentation, and those with less. This suggests a patient profile at higher risk, potentially benefiting from more aggressive immunosuppressive treatment and closer follow-up. Within the spectrum of systemic autoimmune myopathies, this phenotype resembles that of patients with immune-mediated necrotizing myopathy, who typically present with more severe initial symptoms, elevated CPK levels, and a high rate of muscle relapse during immunosuppression tapering [ 14 , 15 ]. A study analyzing muscle biopsies from 26 anti-Jo-1-positive ASyS patients demonstrated that 38.5% exhibited a necrotizing myopathic pattern, which is classically associated with immune-mediated necrotizing myopathies [ 15 ]. Regarding treatment, there was no statistical difference between the muscle relapse group and the non-relapse group, except for the higher use of cyclophosphamide in the latter, likely due to the greater interstitial lung involvement, which is the primary indication for this drug in ASyS [ 16 , 17 ]. The primary limitation of this study lies in its retrospective design conducting at a single center limits the generalizability of the findings. CONCLUSIONS A high frequency of muscle activity relapse was observed in patients with ASyS, particularly among younger individuals exhibiting elevated initial creatine phosphokinase levels and reduced pulmonary involvement. Abbreviations ALT Alanine aminotransferase ASyS Anti-synthetase syndrome ARS Antibodies against aminoacyl-tRNA synthetase AST Aspartate aminotransferase CPK Creatine phosphokinase CT Computed tomography ILD Interstitial lung disease IVIg Intravenous immunoglobulin LDH Lactic dehydrogenase MRC Medical Research Council Declarations ACKNOLEDGMENTS Maria Aurora Gomes da Silva for assistance and support in all laboratory processing. AUTHORS’ CONTRIBUTIONS All authors contributed equally to the writing and reviewing of the manuscript . FUNDING Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq): #139748/2024-5 and #301500/2022-3. AVAILABILITY OF DATA AND MATERIALS Not applicable. ETHICS APPROVAL AND CONSENT TO PARTICIPATE This study was conducted in accordance with the Declaration of Helsinki. The study was approved by the local ethics committee – HCFMUSP – SP (Comitê de Ética - CAAE 34954620.5.0000.0068). CONSENT FOR PUBLICATION Not applicable. COMPETING INTERESTS All authors declare that they have no conflicts of interest. CINICAL TRIAL NUMBER Not applicable. References Monti S, Montecucco C, Cavagna L. Clinical spectrum of anti-Jo-1-associated disease. Curr Opin Rheumatol. 2017;29:612-617. Connors GR, Christopher-Stine L, Oddis CV, Danoff SK. Interstitial lung disease associated with the idiopathic inflammatory myopathies: what progress has been made in the past 35 years? Chest. 2010;138:1464-1474. Behrens Pinto GL, Carboni RCS, Souza FHC, Shinjo SK. A prospective cross-sectional study of serum IL-17A in antisynthetase syndrome. Clin Rheumatol. 2020;39:2763-2771. Cavagna, Trallero-Araguás, Meloni, Cavazzana, Rojas-Serrano, Feist, et al. Influence of antisynthetase antibodies specificities on antisynthetase syndrome clinical spectrum time course. J Clin Med. 2019;8:2013. Huang K, Aggarwal R. Antisynthetase syndrome: A distinct disease spectrum. J Scleroderma Rel Disord. 2020;5:178-191. 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A multidisciplinary approach to the diagnosis of antisynthetase syndrome. Front Med (Lausanne). 2022;9:959653. Lilleker JB, Vencovsky J, Wang G, Wedderburn LR, Diederichsen LP, Schmidt J, et al. The EuroMyositis registry: An international collaborative tool to facilitate myositis research. Ann Rheum Dis. 2018;77:30-39. Marie I, Hatron PY, Dominique S, Cherin P, Mouthon L, Menard JF, Levesque H, et al. Short-term and long-term outcome of anti-Jo1-positive patients with anti-Ro52 antibody. Seminar Arthritis Rheumatism. 2012;41:890-899. Noguchi E, Uruha A, Suzuki S, Hamanaka K, Ohnuki Y, Tsugawa J, et al. Skeletal muscle involvement in antisynthetase syndrome. JAMA Neurology. 2017;74:992–999. Kassardjian CD, Lennon V A, Alfugham NB, Mahler M, Milone M. Clinical features and treatment outcomes of necrotizing autoimmune myopathy. JAMA Neurology. 2015;72:996-1003. Da Silva LMB, Borges IBP, Shinjo SK. High prevalence of necrotising myopathy pattern in muscle biopsies of patients with anti-Jo-1 antisynthetase syndrome muscle biopsies in antisynthetase syndrome. Clin Exp Rheumatol. 2022;41;238-246. Langlois V, Gillibert A, Uzunhan Y, Chabi ML, Hachulla E, Landon-Cardinal O, et al. Rituximab and cyclophosphamide in antisynthetase syndrome-related interstitial lung disease: An observational retrospective study. J Rheumatol. 2020;47:1678-1686. Marco JL, Collins BF. Clinical manifestations and treatment of antisynthetase syndrome. Best Pract Res Clin Rheumatol. 2020;34:101503. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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The primary clinical manifestations include myositis, arthritis, interstitial lung disease (ILD), fever, mechanic\u0026rsquo;s hands, and Raynaud\u0026rsquo;s phenomenon [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe clinical phenotype of ASyS is associated with specific antibody present, as demonstrated in the scientific literature [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. For instance, anti-Jo-1 patients exhibit a higher incidence of myositis, polyarthritis and ILD, whereas anti-PL-12 and anti-PL-7 patients present with a higher incidence of isolated ILD, in addition to increased mortality [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eStudies on ASyS remain limited owing to the rarity of the disease, particularly regarding the description of muscle activity relapses. Retrospective cohorts frequently emphasize joint and lung manifestations due to their diagnostic challenges and the significant impact of ILD on patient survival [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, there has been insufficient characterization of the behavior of muscle manifestations during patient follow-up. Therefore, this study aimed to evaluate the frequency of muscle activity relapse in adult patients with anti-Jo-1 ASyS. Second, to it sought to describe factors associated with these relapses.\u003c/p\u003e"},{"header":"PATIENTS AND METHODS","content":"\u003cp\u003eStudy design. This single-center retrospective cohort study included adult patients with anti-Jo-1 ASyS under regular follow-up at our rheumatology tertiary outpatient clinic between January 2010 and March 2014. The study was approved by the local ethics committee (CAAE 93514918.0.0000.0068).\u003c/p\u003e \u003cp\u003eInclusion criteria. We included adult patients with at least two of the three disorders: joint, lung, and/or muscle involvement. Additionally, the presence of persistent fever, Raynaud\u0026rsquo;s phenomenon and/or \u0026ldquo;mechanic\u0026rsquo;s hands\u0026rdquo; was considered [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, the presence of muscle involvement was mandatory and, as anti-ARS, only anti-Jo-1 autoantibodies were considered in the present study.\u003c/p\u003e \u003cp\u003eExclusion criteria. Patients with incomplete data, patients with overlap syndrome or cancer-associated myositis were excluded.\u003c/p\u003e \u003cp\u003ePatients\u0026rsquo; data. The following pre-standardized and pre-parameterized data were collected from the patients' electronic records:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eDemographic data: age at ASyS\u0026rsquo;s diagnosis, ethnicity, and sex;\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eClinical and laboratory data: disease duration, occurrence of muscle flares, laboratory data, and clinical manifestations at disease onset); the identification of the anti-synthetase autoantibodies [anti-Jo-1, anti-PL-7, anti-PL-12, anti-OJ, and anti-EJ] were determined by a commercially available line blot test kit (Myositis Profile Euroline Blot test kit, Euroimmun, L\u0026uuml;beck, German). Assessment was performed according to a previously established method [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]; muscle involvement and activity were defined as the presence of objective limb muscle weakness - scores of the Medical Research Council - MRC [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], elevated serum levels - at least twice the upper limit - creatine phosphokinase (CPK, reference value: 26\u0026ndash;192 U/L), alanine aminotransferase (ALT, \u0026lt; 31 U/L), aspartate aminotransferase (AST, \u0026lt; 31 U/L), and lactic dehydrogenase (LDH, 135\u0026ndash;214 U/L). Thigh muscle magnetic resonance imaging with identification of muscle edema was also included when available. Myopathic patterns on electroneuromyography and muscle biopsy compatible with inflammatory myopathy were also considered to define muscle involvement. Lung involvement was based on the presence of dyspnea and signs suggestive of pulmonary involvement secondary to ASyS on high-resolution computed tomography (CT) of the chest performed at the initial follow-up. The presence or absence of interstitial lung, ground-glass opacity, or lung fibrosis were considered; joint involvement was defined as nonerosive and nondeforming arthritis; treatment (glucocorticoids, immunosuppressive, immunomodulatory, and immunobiological drugs).\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003eStatistical analysis was conducted. The Shapiro-Wilk test was employed to assess the distribution of each parameter. The results were presented as median (interquartile range: 25th \u0026minus;\u0026thinsp;75th ) for continuous variables, whereas categorical variables were presented as frequency (%). Results were compared using t-Student or Mann-Whitney tests for continuous variables to determine differences between patients with ASyS and the presence or absence of the first muscle disease relapse. Differences in categorical variables were calculated using Fisher\u0026rsquo;s exact test and Pearson\u0026rsquo;s χ\u003csup\u003e2\u003c/sup\u003e test. Differences were considered statistically significant at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Statistical analyses were performed using the SPSS software (version 15.0, Chicago, IL, USA).\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eA total of 95 adult patients diagnosed with ASyS were identified and followed up at our service. Twenty-six patients with non-Jo-1 anti-ARS antibodies or the presence of myositis-associated autoantibodies were excluded. Of the remaining 69 patients, 10 were excluded due to the absence of muscle involvement, and another two were excluded for incomplete data. Thus, the final analysis included 48 adult patients with anti-Jo-1 ASyS.\u003c/p\u003e \u003cp\u003eThe patients had a median age of 44 (35\u0026ndash;57) years, with a predominance of females (81.2%) and individuals of white ethnicity (79.2%). The mean total follow-up time was 80 (26\u0026ndash;126) months.\u003c/p\u003e \u003cp\u003eAmong the 48 patients, 20 experienced new muscle activity (relapse group).\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes the general and initial data of the patients, categorized by the presence (n\u0026thinsp;=\u0026thinsp;20) or absence (n\u0026thinsp;=\u0026thinsp;28) of muscle relapse. Patients with muscle relapses were younger at the time of diagnosis compared to the non-relapse group (P\u0026thinsp;=\u0026thinsp;0.020), with no significant differences observed in terms of sex or ethnicity.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eGeneral and initial feature comparison between ASyS anti-Jo-1 patients with presence or absence of muscle relapse\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMuscle relapse\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo muscle relapse\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003c/p\u003e \u003cp\u003evalue\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at disease onset (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (28\u0026ndash;50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 (40\u0026ndash;57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.020\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (95.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (71.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.061\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhite ethnicity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (75.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (82.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.721\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnosis - symptom\u0026rsquo;s onset (mo)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (3\u0026ndash;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (2\u0026ndash;13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.983\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInitial disease manifestation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMuscle involvement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUpper limb strength\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade V\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.627\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (70.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (71.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (17.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (7.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLower limb strength\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade V\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.707\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (65.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (67.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (17.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (7.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaboratory data\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCPK (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8124 (2746\u0026ndash;13803)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4144 (636\u0026ndash;5975)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAST (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e469 (88\u0026ndash;461)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e228 (43\u0026ndash;246)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.093\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e210 (94\u0026ndash;332)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e252 (39\u0026ndash;169)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.066\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDH (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1180 (649\u0026ndash;1511)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e969 (350\u0026ndash;1219)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.165\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJoint involvement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (65.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (82.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.721\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLung involvement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (85.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (85.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDyspneae\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (80.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (85.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.703\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComputed tomography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInterstitial lung\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (85.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (82.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGround-glass opacity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLung fibrosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (35.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRaynaud phenomenon\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (70.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.546\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (70.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.546\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMechanic\u0026rsquo;s hands\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (65.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (60.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulse therapy with MP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (65.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (30.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.154\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIVIG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.750\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral glucocorticoid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAzathioprine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (60.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMethotrexate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.349\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCyclophosphamide IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (32.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.031\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCyclosporine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.417\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycophenolate mofetil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are expressed as median (25th \u0026ndash; 75th ), or frequency (%).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eALT: alanine aminotransferase; ASyS: anti-synthetase syndrome; AST: aspartate aminotransferase; CPK: creatine phosphokinase; LDH: lactic dehydrogenase; IV: intravenous; IVIG: immunoglobulin; mo: month.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eRegarding the initial clinical manifestations, there were no differences between the groups, nor in the degree of muscle involvement according to the MRC scale. However, a statistically significant difference was found in the initial CPK levels, which were nearly twice as high in the muscle relapse group (P\u0026thinsp;=\u0026thinsp;0.019). The presence of joint disease, ILD, Raynaud\u0026rsquo;s phenomenon, and mechanic\u0026rsquo;s hands was similar between the groups. However, lung involvement, as assessed by chest CT, demonstrated fewer interstitial or fibrotic changes in the non-relapse group (P\u0026thinsp;=\u0026thinsp;0.006). Regarding treatment, both groups received similar therapies, including corticosteroid therapy and oral immunosuppressants. However, the non-relapse group exhibited a higher frequency of intravenous cyclophosphamide use. Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e provides the follow-up data for patients with muscle relapse (n\u0026thinsp;=\u0026thinsp;20), stratified by the number of relapses: single, double, or three or more episodes. This includes clinical and laboratory characterizations of the episodes.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eFollow up of 20 ASyS anti-Jo-1 patients with presence of muscle relapse\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1st muscle relapse\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2nd muscle relapse\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;10)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3rd muscle relapse\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;4)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASyS diagnosis - symptoms (mo)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (15\u0026ndash;38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (15\u0026ndash;73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44 (36\u0026ndash;94)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUpper limb strength\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade V\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (35.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (70.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLower limb strength\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade V\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (80.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (70.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (75.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (25.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaboratory data\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCPK (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e200 (1244\u0026ndash;5278)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2832 (1836\u0026ndash;4488)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3294 (155\u0026ndash;5882)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAST (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66 (43\u0026ndash;190)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e105 (69\u0026ndash;173)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95 (76\u0026ndash;234)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48 (38\u0026ndash;137)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e93 (47\u0026ndash;140)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e60 (49\u0026ndash;136)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDH (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e494 (350\u0026ndash;761)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e594 (430\u0026ndash;851)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e480 (339\u0026ndash;1202)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther disease features\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJoint activity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (75.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLung activity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (35.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (25.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment before new mm symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral glucocorticoid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (60.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (25.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian dose (mg/day)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (9\u0026ndash;33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (20\u0026ndash;45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAzathioprine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (50.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMethotrexate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (35.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (50.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCyclophosphamide IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCyclosporine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycophenolate mofetil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeflunomide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment after new mm symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulse therapy with MP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (65.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (60.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (25.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIVIG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (30.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (25.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral glucocorticoid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAzathioprine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMethotrexate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (25.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCyclophosphamide IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCyclosporine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (50.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycophenolate mofetil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeflunomide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRituximab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (30.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are expressed as median (25th \u0026ndash; 75th ), or frequency (%).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eALT: alanine aminotransferase; ASyS: anti-synthetase syndrome; AST: aspartate aminotransferase; CPK: creatine phosphokinase; LDH: lactic dehydrogenase; IV: intravenous; IVIG: immunoglobulin; mm: muscle; mo: month.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAmong the 20 patients, 10 experienced a second relapse, and four experienced a third episode of muscular activity. Patients with new relapses demonstrated mean CPK levels 14\u0026ndash;16 times above the reference value. Prior to the first muscular episode, only 10 of the 20 patients (50.0%) were receiving oral corticosteroid therapy, with a mean prednisone dose of 13 mg/day in the single-relapse group and 30 mg /day in the multiple-relapse group.\u003c/p\u003e \u003cp\u003eThe most frequently utilized corticosteroid-sparing immunosuppressants were methotrexate, azathioprine, and mycophenolate mofetil. Following the first episode of muscular activity, 13 patients (65.0%) received pulse therapy with methylprednisolone, and six (30.0%) were treated with intravenous human immunoglobulin (IVIg). In subsequent relapse episodes, the utilization of IVIg and rituximab increased.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis study demonstrated that younger anti-Jo-1 ASyS patients, with elevated initial CPK levels and without ground-glass opacities or pulmonary fibrosis on chest CT, are associated with increased muscle activity relapse.\u003c/p\u003e \u003cp\u003eGiven that the clinical presentation phenotype of ASyS varies according to the specific associated antibody [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], this study included only anti-Jo-1-positive patients to enhance sample homogeneity and mitigate confounding factors. Furthermore, anti-Jo-1 was selected due to its higher frequency in ASyS and its association with a higher incidence of myositis compared to non-anti-Jo-1 patients.\u003c/p\u003e \u003cp\u003eThe presence of myopathy is one of the cardinal symptoms of ASyS, characterized by elevated muscle enzymes along with muscle biopsy, muscle magnetic resonance imaging, or electromyography evidence of myositis [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Although myositis may not be present at disease onset, it develops in the majority of ASyS patients over the course of the disease [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe largest cohort described to date of ASyS patients reported a 55.1% prevalence of myositis in anti-Jo1 patients at disease onset, which increased to 82.1% after 72 months of follow-up, with 20% presenting the hypomyopathic form [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Similarly, the Euromyositis registry demonstrated that 90% of anti-ARS-positive ASyS patients exhibited myopathy with muscle weakness [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. This study included only patients with the classic form of myositis, ensuring greater precision in assessing muscle relapses, facilitating relapse measurement, and focusing on the most impactful muscular outcome on patients' quality of life: muscle weakness.\u003c/p\u003e \u003cp\u003eThere are limited studies evaluating muscle relapse in ASyS. Marie et al. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. assessed the characteristics of anti-Jo1 ASyS patients with and without the presence of anti-Ro-52, reporting a muscle recurrence rate of 63.9% in 36 patients from the anti-Ro-52-positive group after a median follow-up period of 33.5 months. The number of relapses ranged from 0 to 3, and 78.3% occurred shortly after therapy tapering. These findings were not statistically significant when compared to the anti-Ro-52-negative group (53 patients). This investigation did not evaluate the factors associated with muscle relapse.\u003c/p\u003e \u003cp\u003eA Japanese cohort evaluated 40 ASyS patients with six different anti-ARS antibodies over an average follow-up period of 39.6 months. Of these, 26 patients (65%) responded to immunosuppressive therapy, demonstrating improved muscle strength and reduced CPK levels. However, muscle relapse was observed in seven patients (26.9%), of whom only one was positive for the anti-Jo-1 antibody [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur study identified a high rate of muscle relapse (42% of patients), particularly in younger patients at diagnosis, those with markedly elevated CPK levels at initial presentation, and those with less. This suggests a patient profile at higher risk, potentially benefiting from more aggressive immunosuppressive treatment and closer follow-up. Within the spectrum of systemic autoimmune myopathies, this phenotype resembles that of patients with immune-mediated necrotizing myopathy, who typically present with more severe initial symptoms, elevated CPK levels, and a high rate of muscle relapse during immunosuppression tapering [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA study analyzing muscle biopsies from 26 anti-Jo-1-positive ASyS patients demonstrated that 38.5% exhibited a necrotizing myopathic pattern, which is classically associated with immune-mediated necrotizing myopathies [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Regarding treatment, there was no statistical difference between the muscle relapse group and the non-relapse group, except for the higher use of cyclophosphamide in the latter, likely due to the greater interstitial lung involvement, which is the primary indication for this drug in ASyS [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe primary limitation of this study lies in its retrospective design conducting at a single center limits the generalizability of the findings.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eA high frequency of muscle activity relapse was observed in patients with ASyS, particularly among younger individuals exhibiting elevated initial creatine phosphokinase levels and reduced pulmonary involvement.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eALT\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Alanine aminotransferase\u003c/p\u003e\n\u003cp\u003eASyS\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Anti-synthetase syndrome\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eARS\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Antibodies against aminoacyl-tRNA synthetase\u003c/p\u003e\n\u003cp\u003eAST\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Aspartate aminotransferase\u003c/p\u003e\n\u003cp\u003eCPK\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Creatine phosphokinase\u003c/p\u003e\n\u003cp\u003eCT\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Computed tomography\u003c/p\u003e\n\u003cp\u003eILD\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Interstitial lung disease\u003c/p\u003e\n\u003cp\u003eIVIg\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Intravenous immunoglobulin\u003c/p\u003e\n\u003cp\u003eLDH\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Lactic\u0026nbsp;dehydrogenase\u003c/p\u003e\n\u003cp\u003eMRC\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Medical Research Council\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eACKNOLEDGMENTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMaria Aurora Gomes da Silva for assistance and support in all laboratory processing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHORS’ CONTRIBUTIONS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed equally to the writing and reviewing of the manuscript\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFUNDING\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq): #139748/2024-5 and #301500/2022-3.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAVAILABILITY OF DATA AND MATERIALS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eETHICS APPROVAL AND CONSENT TO PARTICIPATE\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the Declaration of Helsinki. The study was approved by the local ethics committee – HCFMUSP – SP (Comitê de Ética - CAAE 34954620.5.0000.0068).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONSENT FOR PUBLICATION\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCOMPETING INTERESTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare that they have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCINICAL TRIAL NUMBER\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMonti S, Montecucco C, Cavagna L. Clinical spectrum of anti-Jo-1-associated disease. Curr Opin Rheumatol. 2017;29:612-617.\u003c/li\u003e\n\u003cli\u003eConnors GR, Christopher-Stine L, Oddis CV, Danoff SK. Interstitial lung disease associated with the idiopathic inflammatory myopathies: what progress has been made in the past 35 years? Chest. 2010;138:1464-1474.\u003c/li\u003e\n\u003cli\u003eBehrens Pinto GL, Carboni RCS, Souza FHC, Shinjo SK. A prospective cross-sectional study of serum IL-17A in antisynthetase syndrome. Clin Rheumatol. 2020;39:2763-2771.\u003c/li\u003e\n\u003cli\u003eCavagna, Trallero-Aragu\u0026aacute;s, Meloni, Cavazzana, Rojas-Serrano, Feist, et al. Influence of antisynthetase antibodies specificities on antisynthetase syndrome clinical spectrum time course. J Clin Med. 2019;8:2013.\u003c/li\u003e\n\u003cli\u003eHuang K, Aggarwal R. Antisynthetase syndrome: A distinct disease spectrum. J Scleroderma Rel Disord. 2020;5:178-191.\u003c/li\u003e\n\u003cli\u003eAggarwal R, Cassidy E, Fertig N, Koontz DC, Lucas M, Ascherman DP, et al. Patients with non-Jo-1 anti-tRNA-synthetase autoantibodies have worse survival than Jo-1 positive patients. Ann Rheum Dis. 2014;73:227-232. \u003c/li\u003e\n\u003cli\u003eCavagna L, Nu\u0026ntilde;o L, Scir\u0026egrave; CA, Govoni M, Longo FJL, Franceschini F, Neri R, et al. Clinical spectrum time course in anti-Jo-1 positive antisynthetase syndrome: Results from an international retrospective multicenter study. Medicine. 2015;94:e1144.\u003c/li\u003e\n\u003cli\u003eCruellas MGP, Viana VST, Levy-Neto M, De Souza FHC, Shinjo SK. Myositis-specific and myositis-associated autoantibody profiles and their clinical associations in a large series of patients with polymyositis and dermatomyositis. Clinics (Sao Paulo). 2013;68:909-914.\u003c/li\u003e\n\u003cli\u003eMedical Research Council. Aids to examination of the peripheral nervous system. Memorandum no. 45. London: Her Majesty\u0026rsquo;s Stationary Office; 1976.\u003c/li\u003e\n\u003cli\u003eWells M, Alawi S, Thin KYM, Gunawardena H, Brown AR, Edey A, Pauling JD, et al. A multidisciplinary approach to the diagnosis of antisynthetase syndrome. Front Med (Lausanne). 2022;9:959653.\u003c/li\u003e\n\u003cli\u003eLilleker JB, Vencovsky J, Wang G, Wedderburn LR, Diederichsen LP, Schmidt J, et al. The EuroMyositis registry: An international collaborative tool to facilitate myositis research. Ann Rheum Dis. 2018;77:30-39.\u003c/li\u003e\n\u003cli\u003eMarie I, Hatron PY, Dominique S, Cherin P, Mouthon L, Menard JF, Levesque H, et al. Short-term and long-term outcome of anti-Jo1-positive patients with anti-Ro52 antibody. Seminar Arthritis Rheumatism. 2012;41:890-899.\u003c/li\u003e\n\u003cli\u003eNoguchi E, Uruha A, Suzuki S, Hamanaka K, Ohnuki Y, Tsugawa J, et al. Skeletal muscle involvement in antisynthetase syndrome. JAMA Neurology. 2017;74:992\u0026ndash;999.\u003c/li\u003e\n\u003cli\u003eKassardjian CD, Lennon V A, Alfugham NB, Mahler M, Milone M. Clinical features and treatment outcomes of necrotizing autoimmune myopathy. JAMA Neurology. 2015;72:996-1003.\u003c/li\u003e\n\u003cli\u003eDa Silva LMB, Borges IBP, Shinjo SK. High prevalence of necrotising myopathy pattern in muscle biopsies of patients with anti-Jo-1 antisynthetase syndrome muscle biopsies in antisynthetase syndrome. Clin Exp Rheumatol. 2022;41;238-246.\u003c/li\u003e\n\u003cli\u003eLanglois V, Gillibert A, Uzunhan Y, Chabi ML, Hachulla E, Landon-Cardinal O, et al. Rituximab and cyclophosphamide in antisynthetase syndrome-related interstitial lung disease: An observational retrospective study. J Rheumatol. 2020;47:1678-1686.\u003c/li\u003e\n\u003cli\u003eMarco JL, Collins BF. Clinical manifestations and treatment of antisynthetase syndrome. Best Pract Res Clin Rheumatol. 2020;34:101503.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Anti-synthetase syndrome, inflammatory myopathy, myositis, prognosis, relapse","lastPublishedDoi":"10.21203/rs.3.rs-5876556/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5876556/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo date, no study has analyzed muscular activity relapses in anti-synthetase syndrome (ASyS), underscoring the necessity for this investigation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e. This single-center retrospective cohort study, conducted between 2010 and 2014, included patients with anti-Jo-1 ASyS.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e. A total of 95 patients with ASyS were identified. However, we excluded patients with anti-aminoacyl-tRNA-synthetase non-Jo-1 antibodies (n = 26), or myositis-associated autoantibodies (n = 25), without muscle involvement (n = 10), and those with incomplete data (n = 2). Consequently, a total of 48 anti-Jo-1 ASyS patients were evaluated with a median age of 44 (interquartile range: 35–54) years, predominantly female (81.3%), and of white ethnicity (79.2%). The median follow-up period was 80 (26–126) months. Twenty patients (41.7%) experienced second muscle activity during follow-up, whereas 10 (20.8%) and four (10.4%) experienced third and fourth muscle relapses, respectively. Compared to those without muscle relapse (n = 20), patients with at least one muscle relapse (n = 28) were younger (48 \u003cem\u003evs\u003c/em\u003e. 39 years, respectively; P = 0.020), exhibited a higher median creatine phosphokinase level (4144 \u003cem\u003evs\u003c/em\u003e. 8124U/L; P = 0.019), and demonstrated lower rates of pulmonary involvement, specifically ground-glass opacity (P = 0.006) and lung fibrosis (P = 0.003). There was no significant difference in treatment between patients with and without muscle relapse, except for cyclophosphamide, which was more frequently utilized in patients without muscle relapse (5.0% \u003cem\u003evs\u003c/em\u003e. 32.9%; P = 0.031).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e. A high frequency of muscle activity relapse was observed in patients with ASyS, particularly among younger individuals with high initial creatine phosphokinase levels and reduced pulmonary involvement. A small subset of patients experienced more than three muscle relapses.\u003c/p\u003e","manuscriptTitle":"High frequency of muscle activity relapses in anti-synthetase syndrome","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-28 08:38:43","doi":"10.21203/rs.3.rs-5876556/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f1dbd594-48b7-4ee5-b613-77911d4ae3a0","owner":[],"postedDate":"January 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-02-24T13:08:58+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-28 08:38:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5876556","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5876556","identity":"rs-5876556","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}