[Show abstract][Hide abstract] ABSTRACT: Muscle toxicity is a recognized adverse effect of statin use. Recently, a new myositis syndrome was described in association with antibodies directed against the pharmacologic target of statins, anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR antibody). The patient's genetic background, characteristic histologic patterns (immune-mediated necrotizing myopathy), and presence of anti-HMGCR antibodies define the syndrome. In most patients, statin discontinuation is insufficient to reverse the myositis symptoms, and immunosuppressive therapy is needed. The mechanisms by which these antibodies may lead to disease are not fully elucidated. Several important questions remain unsolved and warrant further research.
Full-text · Article · Oct 2015 · Expert Review of Clinical Immunology
[Show abstract][Hide abstract] ABSTRACT: Objectives:
The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of rare autoimmune diseases characterised by muscle weakness and extramuscular manifestations such as skin rashes and interstitial lung disease. We genotyped 2566 IIM cases of Caucasian descent using the Immunochip; a custom array covering 186 established autoimmune susceptibility loci. The cohort was predominantly comprised of patients with dermatomyositis (DM, n=879), juvenile DM (JDM, n=481), polymyositis (PM, n=931) and inclusion body myositis (n=252) collected from 14 countries through the Myositis Genetics Consortium.
The human leucocyte antigen (HLA) and PTPN22 regions reached genome-wide significance (p<5×10(-8)). Nine regions were associated at a significance level of p<2.25×10(-5), including UBE2L3, CD28 and TRAF6, with evidence of independent effects within STAT4. Analysis of clinical subgroups revealed distinct differences between PM, and DM and JDM. PTPN22 was associated at genome-wide significance with PM, but not DM and JDM, suggesting this effect is driven by PM. Additional suggestive associations including IL18R1 and RGS1 in PM and GSDMB in DM were identified. HLA imputation confirmed that alleles HLA-DRB1*03:01 and HLA-B*08:01 of the 8.1 ancestral haplotype (8.1AH) are most strongly associated with IIM, and provides evidence that amino acids within the HLA, such as HLA-DQB1 position 57 in DM, may explain part of the risk in this locus. Associations with alleles outside the 8.1AH reveal differences between PM, DM and JDM.
This work represents the largest IIM genetic study to date, reveals new insights into the genetic architecture of these rare diseases and suggests different predominating pathophysiology in different clinical subgroups.
Full-text · Article · Sep 2015 · Annals of the rheumatic diseases
[Show abstract][Hide abstract] ABSTRACT: To evaluate a new ultrasound sign, pleural irregularity (PI), for the study of interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) and antisynthetase syndrome (ASS).
The study included patients from our SSc and ASS cohorts with varying degrees of ILD, enrolled from 2011 to 2014. Chest high-resolution computed tomography (HRCT), pulmonary function tests (FVC and DLCO) and chest sonography were performed in each patient. Ultrasound PI and B-lines were quantified using a 72-sonographic point score and HRCT lung abnormalities were quantified using Warrick and Wells scores and categorised through Goh's algorithm. PI was correlated with HRCT and pulmonary function test parameters and its diagnostic performance to detect and classify the extent of ILD was evaluated and compared with B-lines.
Thirty-seven patients were studied, 21 with ASS and 16 with SSc (8 without ILD). PI correlated with the Warrick score both in SSc (r=0.6, p=0.01) and ASS patients (r=0.6, p=0.005), showing a higher performance to detect ILD than using B-lines (p=0.01). In SSc patients PI also correlated with Wells score (r=0.7, p<0.001) and with DLCO (r=-0.5, p=0.05), showing a high diagnostic value for detecting ILD (AUC=0.85, 95% CI 0.64-1) and classifying it into limited or extensive (AUC=0.81, 95% CI 0.57-1). A modification of the Goh algorithm including PI was developed as a screening tool to avoid the use of HRCT in SSc patients without ultrasound evidence of extensive ILD.
PI is useful for evaluation of ILD in SSc and ASS patients, and can be incorporated into a diagnostic algorithm in SSc patients to reducing the need for exposure to ionising radiation.
No preview · Article · Aug 2015 · Clinical and experimental rheumatology
[Show abstract][Hide abstract] ABSTRACT: Idiopathic inflammatory myopathies are a heterogeneous group of rare autoimmune diseases characterized by symmetric proximal muscle weakness and inflammatory infiltrates on muscle biopsy. A meticulously collected combination of clinical, serological, and pathological data is essential to correctly diagnose and classify myositis patients, often a considerable challenge for clinicians. This article provides a comprehensive overview of the most useful tools for the diagnosis and follow-up of patients with myositis. Capillaroscopy, serological biomarkers (particularly the autoantibody profile) and imaging techniques, such as muscle magnetic resonance and chest ultrasound, are of great aid in diagnosing, classifying and managing these patients. Relevant clinical scenarios, such as interstitial lung disease, associated cancer and pregnancy are also addressed in this review. Myositis registries, identification of new autoantibodies, and genetic studies will enhance our understanding of the pathogenesis of these conditions and help to define new diagnostic and therapeutic approaches.
No preview · Article · Apr 2015 · Expert Review of Clinical Immunology
[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to explore whether polymyositis may be considered as an isolated, organ-specific disease or more suitably as a secondary or associated entity. A retrospective re-evaluation of all the muscle biopsies performed at the Hospital Clínic of Barcelona showing histopathological pattern of polymyositis from January 1997 to May 2012 was carried out. The medical records of the patients with the aforementioned pathological pattern were also reviewed. From 1.290 muscle biopsies performed during the period evaluated, 36 with polymyositis pattern were identified. At the time of muscle biopsy, polymyositis pattern was secondary or associated with other disease in 26 patients and was classified as isolated in the remaining ten patients. After pathological re-evaluation and long-term clinical follow-up, only one patient remained with this diagnosis. Overall, the main final diagnosis related to the initial polymyositis pattern was inflammatory myopathy associated with connective tissue disease. Several other associated conditions were also identified. Isolated polymyositis is highly uncommon. Ruling out potential associated or confusing entities, like inclusion body myositis, overlap syndromes, infections, and cancer, is mandatory.
Full-text · Article · Dec 2014 · Rheumatology International
[Show abstract][Hide abstract] ABSTRACT: Objective
The aim of this study is to describe a novel myositis-associated autoantibody (anti-cortactin antibody) and assess related clinical and immunological manifestations and its clinical significance.
Adult patients with myositis (dermatomyositis, polymyositis, immune-mediated necrotizing myopathy, and inclusion body myositis), as well as patients with other autoimmune diseases and non-inflammatory myopathies were analyzed for the presence of anti-cortactin antibody using in-house developed ELISA and immunoblotting techniques with a commercial source of purified cortactin. The cut-off for positive status was determined in a group of healthy volunteers.
Antibody against cortactin was positive in 7/34 (20%) polymyositis patients, 9/117 (7.6%) dermatomyositis, 2/7 (26%) immune-mediated necrotizing myopathy, and none of the 4 patients with inclusion body myositis. The antibody also tested positive in 3/101 patients with other autoimmune diseases (2 systemic sclerosis and 1 systemic lupus erythematosus), and in 1/29 patients with non-inflammatory myopathy. No relevant association with specific clinical features was found in patients with these antibodies. Anti-cortactin antibody was more frequently positive in patients with polymyositis and immune-mediated necrotizing myopathy than in the remaining myositis patients, and was the only myositis autoantibody found in sera of 3 patients from these groups.
Our data indicate that cortactin is a novel target antigen in patients with autoimmune diseases, especially patients with polymyositis or immune-mediated necrotizing myopathy. Anti-cortactin can be considered a new myositis-associated antibody.
Full-text · Article · Oct 2014 · Autoimmunity Reviews
[Show abstract][Hide abstract] ABSTRACT: The aim of this article is to study the evidence-based knowledge related to the use of biological therapies in patients diagnosed with idiopathic inflammatory myopathy (dermatomyositis, polymyositis and inclusion body myositis). In this review the leading published studies related to the use of biological therapy in patients with myositis are analysed; mainly those with high methodological standards, that means randomized and controlled studies. Methodological drawbacks due to the rarity and heterogeneity of these complex diseases are also addressed. Up to now is not possible to ascertain the biologics as a recommended therapy in patients with myositis, at least based in the current evidence-based knowledge, although it can not be neglected as a therapeutic option in some clinical situations, taking into account the scarce of effective treatments in those patients, especially in refractory myositis. Future studies probably will help to better define the role of biological therapies in patients with idiopathic inflammatory myopathy.
No preview · Article · Sep 2014 · Medicina Clínica
[Show abstract][Hide abstract] ABSTRACT: Objective
To establish the clinical course of interstitial lung disease (ILD) in scleroderma related to the presence of anti-PM/Scl antibody compared with anti-Scl-70 in a Spanish cohort. Furthermore, no study has thoroughly investigated the outcome of pulmonary function test in the first group of patients.
Sixty-three Spanish patients with scleroderma and ILD were selected in a retrospective observational study. Fourteen were positive for anti-PM/Scl antibodies and forty-nine for anti-Scl-70. Clinical assessments, including pulmonary function test, were collected. Variations equal or greater than 10% in forced vital capacity (FVC) were considered significant. Progression-free survival of disease was defined as the period of stable illness since pulmonary fibrosis diagnosis.
Anti-Scl-70 patients had a higher frequency of diffuse SSc subset, peripheral vasculopathy and gastrointestinal involvement. Inflammatory myopathy was associated to anti-PM/Scl antibody. Anti-PM/Scl patients presented more improvement in FVC during follow-up: 30.8%, compared to a 7.1% in Scl-70 group (P = 0.04), with less worsening of this parameter (15.4% vs. 52.4% in Scl-70 patients, P = 0.01), and secondary less frequency of severe restrictive pattern (FVC < 50%) (7.7% compared to 42.9% in the other group, P = 0.02). Regarding treatment, more anticalcineurinics were used in anti-PM/Scl patients while cyclophosphamide and mycophenolate were mainly used in anti-Scl-70. The progression-free survival of disease was higher in anti-PM/Scl patients, with 76% at 10 years from diagnosis of ILD against a 29% in Scl-70 group.
Several features and prognosis of ILD in SSc may be modified depending on the identified immunological profile.
No preview · Article · Jul 2014 · Seminars in Arthritis and Rheumatism