ORIGINAL RESEARCH Patients with pure dermatomyositis/polymyositis and anti-PM/Scl autoantibody resembling anti-synthetase syndrome Samara Pereira AlvesI, Marilda Guimarães SilvaI, Isabela Bruna Pires BorgesI, Samuel Katsuyuki ShinjoI I Universidade de São Paulo, Faculdade de Medicina FMUSP, Division of Rheumatology, São Paulo, Brazil. OBJECTIVE: The anti-PM/Scl autoantibody has been described in patients with scleromyositis. However, there are scant studies evaluating its prevalence and reactivity in dermatomyositis and polymyositis. METHOD: A cross-sectional, single center study evaluating the anti-PM/Scl autoantibody in 85 dermatomyositis and 32 polymyositis patients, without overlapping syndrome, was conducted between 2000 and 2016. Clinical data and complementary examinations were reviewed from electronic medical records with pre-parameterized information. RESULTS: The mean age of dermatomyositis and polymyositis patients was 41.1 and 42.8 years, respectively. The presence of anti-PM/Scl was observed in 5 (5.9%) dermatomyositis and 2 (6.3%) polymyositis patients. Two of these patients also had the anti-Ku antibody. The relevant clinical manifestations of these 7 patients were constitutional symptoms (100% of cases), muscular (100%), pulmonary (85.7%) and joint (71.4%) involvement, “mechanic hands” (85.7%), Raynaud phenomenon (85.7%) and plantar hyperkeratosis (85.7%). The 7 patients had relapses of disease activity, but at conclusion of the present study, 5 had complete clinical response and 2 complete remission of the disease. CONCLUSION: There is a low frequency of the anti-PM/Scl autoantibody in dermatomyositis and polymyositis patients. In addition, patients with this autoantibody exhibit a similar pattern of manifestations to that of antisynthetase syndrome. KEYWORDS: Autoantibodies; dermatomyositis; myositis; polymyositis. Alves SM, Silva MG, Borges IBP, Shinjo SK. Patients with pure dermatomyositis/polymyositis and anti-PM/Scl autoantibody resembling anti- synthetase syndrome. MedicalExpress (São Paulo, online). 2018;5:mo18002 Received for Publication on January 28, 2018; First review on February 26, 2018; Accepted for publication on March 2,2018; Online on March 16, 2018 E-mail: [email protected] INTRODUCTION The anti-PM/Scl antibody is considered to be ■ associated with myositis and is typically described Dermatomyositis (DM) and polymyositis (PM) in patients with overlap syndrome, such as systemic are autoimmune systemic myopathies that primarily sclerosis and autoimmune myositis.3-12 affect skeletal muscle. In the case of DM, there is also This autoantibody has also been described in few a cutaneous involvement, including the classic lesions cases of DM or PM without overlapping syndrome.4,5,7,8,11-19 known as heliotrope and Gottron’s papules.1,2 Extra- However, in this context, the autoantibody was correla- muscular manifestations may also occur, with joint, ted with the presence of interstitial lung disease,11,13,17-19 cardiac, pulmonary and/or gastrointestinal tract neoplasia7,13,16,18,19 or palmar and/or plantar hyperkera- involvements.2 tosis.11,13,17-19 However, the few study available have many DOI: 10.5935/MedicalExpress.2018.mo.002 limitations and it is therefore difficult to determine Copyright © 2016 MEDICALEXPRESS. This is an open access article distributed under the terms of the creative commons attribution Non-Commercial License (creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non commercial use, distribution and reproduction in any medium, provided the original work is properly cited. 1 MedicalExpress (São Paulo, online). 2018;5:mo18002 Anti-PM/Scl in isolated myositis Alves SP the true prevalence and reactivity of the anti-PM/Scl papule, facial rash, “V-neck” sign, “shawl” sign, periungual autoantibody in this population. For instance, previous hyperemia, vasculitis, calcinosis, ulcers, Raynaud’s studies failed to evaluate and/or exclude patients phenomenon, palmar/digital hyperkeratosis (“mechanic with (a) anti-MDA-55,7,8,11-16,18,19 and/or antisynthetase hands”) and plantar hyperkeratosis, muscle weakness of autoantibodies (anti-Jo-1, EJ, JO, PL-7 and/or PL-12),7,11- upper and lower limbs, dysphagia and pulmonary (dyspnea: 14,16,18,19 (b) clinically amyopathic DM,5,7,8,11-19 (c) patients moderate to low effort, rapid evolving dyspnea: less than 3 with lung diseases,5,7,8,11-19 (d) smokers (5,7,8,11-19), (e) months after onset of general symptoms); neoplasias,7,13,16,18,19 among others. 3. Changes on high-resolution computer tomography Therefore, the primary objective of the present images of the lung: incipient pneumopathy, “ground glass” study was to evaluate the prevalence of the anti-PM/Scl autoantibody in a large number of patients with pure DM 4. Serum levels of muscle enzymes in blood or PM, addressing previous study limitations. A secondary samples(opacity) taken and pulmonary routinely for fibrosis medical in consultation:both lung bases. creatine aim was to evaluate a possible association between this phosphokinase (reference value: 32-294 U/L), and aldolase autoantibody and the clinical and laboratory evaluations (1.0-7.5 U/L). as well as the complementary exam parameters of patients Recurrences of PM/DM were diagnosed on the basis with DM and PM. of the following criteria: clinical relapse (i.e. muscle and/or dermatological manifestations); biochemical relapses (i.e. increase of serum muscle enzymes for which there was no ■ PATIENTS AND METHODS other explanation). A complete clinical response was considered after A cross-sectional, single-center study evaluating the a 6-month continuous period of no evidence of disease presence of the anti-PM/Scl autoantibody in adult patients activity while still receiving myositis therapy. Clinical the criteria of Bohan and Peter1 was conducted. All patients with definite DM or PM (defined or probable) according to with no evidence of disease activity while not receiving any evaluated were seen at our tertiary service between 2000 remission was defined as the 6-month continuous period and 2016. clinical and/or laboratory disease activity.21 This study was approved by the institutional Ethics myositisSerum therapy. samples Relapsing stored was at -20ºCdefined were as anycollected renewed for Committee. the analysis of the autoantibodies at the time of the initial Exclusion criteria were the presence of associated investigation of the active disease (laboratory and clinical). systemic autoimmune diseases (overlap syndrome) - anti-syntheses (anti-Jo-1, PL-7, PL-12, OJ and EJ), anti-SRP, sclerodactilia, telangiectasias), neoplasia, pulmonary anti-KuIdentification and anti-Mi-2 of the anti-PM/Scl were performed autoantibody, using a commercialas well as of infectionsincluding systemic (turberculosis, sclerosis aspergilloma) (skin hardening and (fibrosis), chronic obstructive pulmonary disease, history of smoking, the manufacturer’s protocol. The evaluation of the results suspected cases of other myopathies (muscular dystrophies, waskit (Myositis based on Profile the methods 3, Euroimmun, established Germany) in a previous according study. to22 metabolic myopathies and necrotizing immune-mediated myopathies), clinically amyopathic DM, and positivity was performed using the Enzyme-linked immunosorbent for anti-Scl70, anti-centromere, rheumatoid factor, assayIn the (ELISA) case of method,the anti-MDA-5 through autoantibody,recombinant MDA-5 identification and the antisynthetase (anti-Jo-1, PL-7, PL-12, OJ or EJ), anti-MDA-5, anti-MDA-5 monoclonal antibody (MyBioSource, CA, USA). anti-SRP or anti-HMGCR autoantibodies. Results were evaluated according to methods established Of the initial 340 patients, 223 were excluded after in a previous study.23 Anti-HMGCR antibody was assayed applying the exclusion criteria. Thus, 117 consecutive by enzyme-linked immunosorbent assay (ELISA), using patients were analyzed: 85 (72.7%) DM and 32 (27.3%) recombinant HMGCR protein and anti-HMGCR polyclonal PM patients. antibody (MyBioSource, CA, USA). For the purposes of this The following data on eligible patients were evaluated study, patients with anti-HMGCR values greater than three from electronic medical records, with pre-standardized and standard deviations from the mean of 8 healthy individuals parameterized information. The following information on were considered positive. The rheumatoid factor was the initial diagnostic investigation in patients with clinical- assayed by the nephelometry method. laboratory activity was assessed: Statistical analysis. The Kolmogorov-Smirnov 1. Demographics: age at disease diagnosis, time test was used to evaluate the distribution of each of the between diagnosis and symptoms onset, gender and continuous variables. The results were expressed as mean ethnicity. ± standard deviation for continuous variables, and number 2. Clinical manifestations: constitutional symptoms (%) for categorical variables. Median values (interquartile (fever and weight loss), heliotrope, Gottron’s sign/ 25th - 75th) were calculated for continuous variables that did not have a normal distribution. 2 Anti-PM/Scl in isolated myositis MedicalExpress (São Paulo, online). 2018;5:mo18002 Alves SP 1 RESULTS possible DM, according to the criteria of Bohan and Peter, as ■ well as patients with other autoimmune systemic diseases, A total of 85 (72.7%) DM and 32 (27.3%) PM patients thus avoiding any possible selection bias. were included. Demographic, clinical, laboratory and Available studies4,5,7,8,11-19 have evaluated the complementary