[Classification of idiopathic inflammatory myopathies based on clinical manifestations and myositis-specific antibodies].
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OBJECTIVE To investigate the classification of idiopathic inflammatory myopathies (IIM) based on clinical manifestations and myositis- specific antibodies using cluster analysis. METHODS We retrospectively analyzed the data of patients with IIM admitted in Nanfang Hospital in 2015-2019. The clinical data of the patients including serum creatine kinase (CK), interstitial lung disease (ILD), cancer, and myositis-specific antibodies were collected for two-step cluster analysis to identify the distinct clusters of patients, whose clinical characteristics were subsequently analysed. RESULTS A total of 71 patients with IIM were included in this study, including 30 (42.3%) with polymyositis (PM), 20 (28.2%) with classic dermatomyositis (DM), 16 (22.5%) with amyopathic dermatomyositis (CADM), and 5 (7.0%) with immune-mediated necrotizing myopathy (IMNM). Two-step cluster analysis identified 3 distinctive subgroups: Cluster 1 of 15 (51.7%) patients characterized by rash, positive anti-MDA5 antibody and hypoproteinemia (P < 0.05) with normal or slightly elevated CK level, mainly corresponding to CADM; Cluster 2 of 4 (57.1%) patients with significantly elevated CK and positive anti-SRP antibody (P < 0.001) corresponding to IMNM; and Cluster 3 of 17 (48.6%) patients consisting primarily of patients with PM, characterized by positivity for anti- aminoacyl transfer RNA synthetases antibodies (P=0.022) corresponding to antisynthetase syndrome (ASS). CONCLUSIONS Patients with IIM can be divided into 3 subgroups based on their clinical and serological characteristics (especially myositis-specific antibodies), and among them ASS may represent an independent IIM subgroup with unique clinical characteristics.Keywords:
Creatine kinase
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Background: Idiopathic inflammatory myopathies (IIM) are a group of rare diseases consisting on immune-mediated muscle damage. About 40 to 60% show specific-myositis antibodies; aditionally, 20-40% can show myositis-related (non-specific) antibodies. The profile of antibodies can help to divide patients into subgroups with more homogeneous clinical characteristics and prognosis. Objectives: This study characterizes patients with IIM with specific or related anti-myositis antibodies, in five hospitals in the Alicante health area. Methods: This is an observational study, carried out in five hospitals with a reference population of 1.083.463 people. Patients with positive anti-myositis antibodies between October 2015 and May 2018 were selected from the database of the Clinical Laboratory of the University Hospital of Alicante. We considered the following antiboides: anti-myositis specific antibodies (anti-TIF1y, anti-MDA5, anti-Mi-2, anti-PmScl75, anti-PMScl100, anti-NXP2, anti-SRP), anti-synthetase antibodies (anti-PL7, anti-PL12, anti-Jo1, anti-OJ), myositis-related antibodies (anti-Ro52, anti-Ku). Clinical records were examined, identifying those patients with a diagnosis of IIM acording to their clinician, rheumatologist. Epidemiological and clinical data were obtained. Results: 291 patients with positive anti-myositis antibodies were identified. Among them, 40 patients had a diagnosis of IIM. Median age was 59.5 (IQR 41.5, 70) years and 68% were women. Within the subgroups, the most frequent diagnosis were dermatomyositis (n=22; 55%) and polimyositis (n=9; 22%). The most common antibody detected was anti-TIF-y among specific antibodies, and anti-Jo-1 among the anti-synthetase antibodies. The most common extramuscular feature was skin involvement. The presence of interstitial lung disease was reported in about one third of patients, being UIP the most commong pattern. Regarding treatment, the use of steroids was generalized; methotrexate was the most used inmunosupresant agent. Eight patients had a cancer related myopathy. DM (N=22 ) PM (n=9 ) DMJ (N=3 ) IMNM (n=1 ) AS (n=5 ) Age, median (IQR ) 65,5(46, 76) 57(34, 66) 15,7 (14, 18) 83 (-) 61(56, 64) Female n(% ) 15(68,2) 6(66,6) 2(66,6) 1(100) 3(60) Muscular feat. n(% ) 16(77,7) 9(100) 1(33,3) 1(100) 5(100) ILD n(% ) 1(4,5) 3(33,3) 0 0 5(100) Disfagia n(% ) 3(13,6) 1(11,1) 0 0 0 Skin feat n(% ) 17(77,3) 0 2(66,6) 0 1(20) arthritis n(% ) 1(4,5) 0 2(66,6) 0 4(80) Raynaud n(% ) 4(19) 1(11,1) 0 0 1(20) Calcinosis n(% ) 1(4,5) 1(11,1) (66,6) 0 0 Puffy hands n (% ) 2(9) 0 0 0 2(40) Sicca synd n(% ) 3(13,6) 1(11,1) 0 0 0 Cáncer n(% ) 7(31,8) 1(11,1) 0 0 0 Ck máx(UI/l), median (IQR ) 432(171, 706) 809(350, 1653) - - 665(396, 2300) Conclusion: This register allows us to characterise patients with inflammatory myositis in our area. It is important to make multicentric and prospective registers in infrequent diseases such as IIM in order to have more detailed and representative information about clinical and socio-demographic characteristic as well as prognostic data from these patients. References: [1]Dalakas M. Inflammatory Muscle Diseasees. N Engl J Med 2015;372:1734-47. [2]Lündberg IE, Tjärnlund A, Bottai M, et al. 2017 Ann Rheum Dis2017;76:1955–1964. [3]Betteridge Z, McHugh N. J. Intern Med, 2016 Jul;280(1):8-23. [4]Nuño L et al. Reumatol Clin. 2017;13(6):331-337 [5]Lilleker JB, Vencovsky J, Wang G, et al.. Ann Rheum Dis 2018;77:30-39 Disclosure of Interests: None declared
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Background.In recent years, many novel myositis-specific autoantibodies (MSAs) have been identified.However, their links with the pathogenesis and clinical manifestations of inflammatory myopathies remain uncertain. Objectives.To characterize the population of adult dermatomyositis (DM) and polymyositis (PM) patients treated at our center for autoimmune diseases using clinical and laboratory measures. Materials and methods.According to the Bohan and Peter criteria, we retrospectively analyzed patients who fulfilled diagnostic criteria for DM or PM.Myositis-specific autoantibodies and myositis-associated autoantibodies (MAAs) were identified using immunoblot assays.Results.Fifty-one PM (71% women) and 36 DM (67% women) Caucasian patients with a median age of 58 (range: 21-88) years who met the definite or probable diagnostic criteria for myositis were included in the study.Myositis-specific autoantibodies were identified in 63 (72%) patients, whereas MAAs were observed in 43 (49%) of them.Interstitial lung disease (ILD) was characteristic of PM patients (67%, χ 2 with Yates's correction (χ c 2 ) = 13.8078,df = 1, p = 0.0002), being associated with anti-Jo-1 or anti-PL-12 antibodies (fraction comparison test (FCT) 6.4878, p < 0.0001, 6.8354, p = 0.0003, respectively).Interestingly, among patients with anti-MDA5 antibodies (n = 8, 9.2%), all but one had an amyopathic form, with more frequent ILD, skin changes and arthralgias than observed in other patients (FCT 4.7029, p = 0.0228 and p = 7.7986, p = 0.0357, p = 4.7029 and p = 0.0228, respectively).Anti-signal recognition particle (SRP) was strongly associated with the Raynaud's phenomenon (FCT 4. 1144, p = 0.0289) and the highest muscle injury markers (Mann-Whitney U test, z = 2.5293, p = 0.0114).Malignancy was recorded in 14 (16%) patients and was equally common in those with PM and DM.The anti-TIF-1γ was the most frequently related to cancer χ 2 = 14.7691, df = 1, p < 0.0001).The anti-Mi-2α, similarly prevalent in DM and PM, was typically accompanied by skin changes (FCT 7.7986, p = 0.0357) but not ILD (FCT 8.7339, p = 0.0026). Conclusions.Identification of MSAs might help to predict the clinical course of the autoimmune myopathy and malignancy risk.However, these antibodies were absent in about 30% of patients with typical PM or DM manifestations, which encourages further research in this area.
Overlap syndrome
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Objectives Myositis-specific autoantibodies (MSAs) are useful tools for identifying clinically homogeneous subsets and predicting prognosis of patients with idiopathic inflammatory myopathies (IIM) including polymyositis (PM) and dermatomyositis (DM). Recent studies have shown that anti-NXP2 antibody (Ab) is a major MSA in juvenile dermatomyositis (JDM). In this study the frequencies and clinical associations of anti-NXP2 Ab were evaluated in adult patients with IIM. Methods Clinical data and serum samples were collected from 507 adult Japanese patients with IIM (445 with DM and 62 with PM). Eleven patients with JDM, 108 with systemic lupus erythematosus, 433 with systemic sclerosis and 124 with idiopathic pulmonary fibrosis were assessed as disease controls. Serum was examined for anti-NXP2 Ab by immunoprecipitation and western blotting using polyclonal anti-NXP2 Ab. Results Seven patients (1.6%) with adult DM and one (1.6%) with adult PM were positive for anti-NXP2 Ab. Except for two patients with JDM, none of the disease controls were positive for this autoantibody. Among eight adult patients with IIM, three had internal malignancies within 3 years of diagnosis of IIM. Another patient with DM also had a metastatic cancer at the diagnosis. All of the carcinomas were at an advanced stage (stage IIIb–IV). Conclusions While less common than in juvenile IIM, anti-NXP2 Ab was found in adult IIM. Anti-NXP2 Ab may be associated with adult IIM with malignancy.
Juvenile Dermatomyositis
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Few studies have investigated the prognostic factors for idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) across different clinical/serological phenotypes.We conducted a retrospective analysis of patients diagnosed with IIM between January 2012 and December 2017.Of the 760 IIM cases registered, 679 adult cases were included in this study. ILD was present in 508 cases, and the presence of ILD in the clinically amyopathic DM, DM and PM groups was 92.7, 73.6 and 55.1%, respectively (P < 0.01). The prevalence of ILD in the anti-synthetase antibody (ASA)+-IIM group was higher than that in ASA--IIM group (95.2 vs 72.4%, P < 0.01); no such difference was found between the anti-histidyl-tRNA synthetase (Jo-1)+-IIM and Jo-1-ASA+-IIM groups (93.0 vs 98.5%, P > 0.05). The prevalence of ILD in the melanoma differentiation-associated protein-5 (MDA-5)+-IIM group was higher than that in MDA-5--IIM group (97.8 vs 72.1%, P < 0.01). Among adults with IIM, men with concurrent ILD, who were older than 50 years, were most likely to die. No significant difference was found in the all-cause mortality rates between DM-ILD and clinically amyopathic DM-ILD groups (33.3 vs 23%, P > 0.05), although both were higher than that in PM group (13.2%, P = 0.01 and P < 0.05, respectively). No difference was found in the all-cause mortality rates between MDA5-ASA--IM-ILD and MDA5-ASA+-IM-ILD groups (17.2 vs 12.8%, P > 0.05), and both were lower than that in MDA5+ASA--IM-ILD group (33.7%, P < 0.05).The prevalence of ILD in IIM and the prognosis of IIM-ILD patients may vary depending on the statuses of the ASA and MDA-5 antibodies.
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Background: The idiopathic inflammatory myopathies (IIM) are characterized by muscle weakness, skin disease and various internal organ involvement and they can overlap with other autoimmune diseases. Recent autoantibody panels improve understanding and management of inflammatory myopathies. Myositis specific autoantibodies including Anti-TIF-1, Anti-NXP2, Anti-MDA5, Anti-SAE1, anti-HMGCR and anti-cN1A are regarded as key biomarkers aiding the diagnosis of patients. On the other hand, myositis-associated autoantibodies (MAAs) are also found in other autoimmune rheumatic diseases. Objectives: To investigate the clinical meaning and impact of new myositis autoantibodies panel in real life data. Methods: A total of 110 subjects (77 female, 33 male) admitted to Hacettepe University Hospitals with the signs and symptoms of IIM were screened by a line immunoblot assay (EUROLINE: Autoimmune Inflammatory Myopathies16 Ag) between 2017 and 2020. Only moderate or strong reactivity results were reported as positive. Demographic, clinical, laboratory, therapeutic data and imaging features were obtained by the retrospective review of medical records. IIM patients were diagnosed by Bohan and Peter’s criteria and classified according to the EULAR/ACR classification criteria for adult and juvenile IIM and their major subgroups. Results: IIM was diagnosed in 61 patients (42.6% DM/JDM and 57.4% PM) and patients with overlap were in decreasing order, Scleroderma (n=8), RA (n=5), Sjogren (n=4), SLE (n=3), autoimmune hepatitis (n=2). Myositis-specific autoantibodies (MSAs) were found in 60%, myositis-associated autoantibodies (MAAs) in 41% of inflammatory myositis patients. The most common MSAs were anti-Jo-1 (16.4%) and anti-MDA-5 (13.1%) and the most common MAA was Ro-52 (32.7%) (Table 1). MAAs were more common in patients with polymyositis (54% vs 23% p=0.013). Twenty-one (34.4%) patients (61.0% females) had interstitial lung disease (ILD). Anti-Jo-1 (38.1%) and anti-Ro-52 (52.4%) was the most common MSA and MAA in patients with IIM and ILD. MSAs were also determined in 10 of the 49 patients who were not diagnosed with IIM. Five patients with Anti-SRP, Anti-Mi-2 alpha, Anti-Jo-1 Anti-PL7, Anti-MDA-5 autoantibodies diagnosed as connective tissue disorder, one of them also had bladder cancer. Three patients with Anti-NXP2, Anti-PM-Scl 75, Anti-Ro-52, Anti-Mi-2 beta, Anti-PL7, Anti-PL12 autoantibodies had ILD. One patient (Anti-Mi-2 alpha, Anti-NXP2 and Anti-Ku autoantibodies positive) had viral myositis and one patient (Anti-Mi-2 alpha, Anti-Ro-52 autoantibodies positive) had inflammatory polyneuropathy. Conclusion: Our study revealed relationship of anti-Jo-1 and anti-Ro-52 but not anti-MDA-5 in ILD-inflammatory myopathies. Even though new autoantibodies panel give opportunity to a closer look for inflammatory myopathies, larger series of patients should be evaluated to determine the association of specific antibodies in the differential diagnosis and prediction of outcome of IIM. MSA positivity in non-IIM diagnosed patients should be monitored to determine whether this positivity is related to a future disease development. Disclosure of Interests: Gözde Kübra Yardimci: None declared, Enes Erul: None declared, Emre Bilgin: None declared, Bayram Farisoğullari: None declared, Levent Kiliç: None declared, Zeynep Saribas: None declared, Umut Kalyoncu Consultant of: Abbvie, Amgen, Janssen, Lilly, Novartis, UCB, Ali Akdoğan: None declared, Burcin Sener: None declared, Şule Apraş Bilgen: None declared, Omer Karadag: None declared
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myalgia
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Background
SinceBohan and Peter first described their diagnostic criteria foridiopathic inflammatorymyopathies (IIM) in 1975, new discoveries suchas myositis-specific and myositis-associated autoantibodies (Abs) have been made.Objectives
To investigate correlations between specificmyositis Abs and their frequenciesand clinical associationsacross different IIM groups, collectively demonstrating theutility of the new clinicoserologic classification in Koreanadult patients with IIM.Methods
We conducted a multicenter cohort study including 67adult patients (age≥18 years) who have been diagnosed as IIM by ENMC criteria.Immunoblot assay with Euroline strip(EUROIMMUN, Germany)was performed using the sera of definite deramatomyositis (DM, n=36), definite polymyositis (PM, n=25), amyopathic DM (n=4), DM sine dermatitis (n=1), and immune mediated necrotizing myopathy (IMNM, n=1). Patients were classifiedbased on three classifications: 1) novel clinicoserologic classification suggested by Troyanov et al. in 2017. 2) 2017 EULAR/ACR classification criteria. 3) 2004 European neuromuscular center (ENMC) criteria.Associations ofmyositis Absand clinical subsets of IIM were investigated.Results
The distribution of the various IIM differed strikingly from those using the 3 classifications (Fig1). According to the 2004 ENMC classification and 2017 EULAR/ACR classification criteria, DM and PM was the most and the second frequent entities (DM: 55.2%, 56.7%; PM: 35.8%, 37.3%). But, using the new clinicoserologic classification,overlapmyositis(OM) is the major type of IIM and the frequency of PM is significantly decreased.Anti-ARS Abs specificity included anti-Jo-1(16.4%), -OJ(4.6%), -EJ(6.2%) -PL-7(3.1%), and -PL-12(4.6%). Interstitial lung disease was closely associated with anti-MDA5,and anti-ARS Abs, while DM-specific skin lesion was frequently observed in patients with anti-TIF1γ and anti-ARS Abs. Sevenpatients with cancer-associated DM were identified. They were positive for anti-TIFγ (5/7) and anti- SRP(3/7) (table 1).Conclusion
Novel classification based on distinctive features and new myositis Absreflects the clinical phenotype of IIM better. Establishment of a system routinely available to screen myositis Abs is needed. Thiswill be beneficial to providemore precise diagnosis and proper management for patients with IIM.Reference:
[1] Jean-Luc Senecal, Jean-Pierre Raynauld, Yves Troyanov. A New Classification of Adult Autoimmune Myositis. Arthritis Rheum2017;69:878-884.Disclosure of Interests
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