Sporadic inclusion body myositis (sIBM) is a rare disease that is difficult to diagnose. Muscle biopsy provides three prominent pathological findings: inflammation, mitochondrial abnormalities and ...fibber degeneration, represented by the accumulation of protein depots constituted by β-amyloid peptide, among others. We aim to perform a screening in plasma of circulating molecules related to the putative etiopathogenesis of sIBM to determine potential surrogate biomarkers for diagnosis. Plasma from 21 sIBM patients and 20 age- and gender-paired healthy controls were collected and stored at -80°C. An additional population of patients with non-sIBM inflammatory myopathies was also included (nine patients with dermatomyositis and five with polymyositis). Circulating levels of inflammatory cytokines (interleukin IL-6 and tumor necrosis factor TNF-α), mitochondrial-related molecules (free plasmatic mitochondrial DNA mtDNA, fibroblast growth factor-21 FGF-21 and coenzyme-Q10 CoQ) and amyloidogenic-related molecules (beta-secretase-1 BACE-1, presenilin-1 PS-1, and soluble Aβ precursor protein sAPPβ) were assessed with magnetic bead-based assays, real-time polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA) and high-pressure liquid chromatography (HPLC). Despite remarkable trends toward altered plasmatic expression of inflammatory and mitochondrial molecules (increased IL-6, TNF-α, circulating mtDNA and FGF-21 levels and decreased content in CoQ), only amyloidogenic degenerative markers including BACE-1, PS-1 and sAPPβ levels were significantly increased in plasma from sIBM patients compared with controls and other patients with non-sIBM inflammatory myopathies (
< 0.05). Inflammatory, mitochondrial and amyloidogenic degeneration markers are altered in plasma of sIBM patients confirming their etiopathological implication in the disease. Sensitivity and specificity analysis show that BACE-1, PS-1 and sAPPβ represent a good predictive noninvasive tool for the diagnosis of sIBM, especially in distinguishing this disease from polymyositis.
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.
Abstract Objective The objective of this article was 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. Methods A total of 63 Spanish patients with scleroderma and ILD were selected in a retrospective observational study. Among them, 14 were positive for anti-PM/Scl antibodies and 49 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. Results 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 patients. 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 the Scl-70 group. Conclusions Several features and prognosis of ILD in SSc may be modified depending on the identified immunological profile.
Abstract Background and purpose Idiopathic inflammatory myopathies (IIM) are systemic diseases, characterized by the presence of an inflammatory muscle infiltrate. Although more frequent in women, ...its relationship with pregnancy has not been extensively studied. Our goal was to analyze the interaction between pregnancy and myositis in a cohort of IIM women from a single center. Methods A total of 51 patients from a historical cohort of IIM diagnosed between 1983 and 2013 were interviewed with a specific questionnaire. Comparisons between pregnancies occurring before and after the onset of the disease were performed using generalized mixed-effect models with normal and binomial distributions adjusted for confounding factors and clustering. Results A total of 102 pregnancies from 51 patients (41 with dermatomyositis and 10 with polymyositis) were analyzed. A total of 14 pregnancies from 8 patients occurred after disease onset; statistically significant ( p = 0.02) clinical improvement during gestation was evident in 7 pregnancies (4 patients), 5 of them (from 2 patients) experienced a relapse of IIM symptoms afterwards, while in the rest, there was no influence of pregnancy on the disease. No disease flare associated with pregnancy was observed. Two patients were diagnosed within the first 6 months after delivery and none during pregnancy. No evidence was found to support pregnancy as a trigger for myopathy ( p = 0.71). Conclusions Pregnancy does not seem to carry a worse prognosis for the mother nor for the fetus in patients with IIM; on the contrary, nearly half of the patients in our series improved clinically when they became pregnant, a relapse of IIM symptoms being common afterwards. Pregnancy does not appear to be a trigger for IIM.
Anti-synthetase syndrome (ASSD) is a heterogeneous autoimmune disease characterised by multi-system involvement with a wide variety of manifestations. Validated classification criteria are necessary ...to improve recognition and prevent misclassification, especially given the lack of reliable and standardised autoantibody testing. We systematically reviewed the literature to analyse proposed ASSD criteria, characteristics, and diagnostic performance.
We searched PubMed and Embase databases (01/01/1984 to 06/11/2018) and the ACR and EULAR meeting abstracts (2017-2018). Sensitivities, specificities, positive, negative likelihood ratios and risk of bias were calculated for ASSD criteria and key variables reported in the literature. We performed meta-analysis when appropriate.
We retrieved 4,358 studies. We found 85 proposed ASSD criteria from a total of 82 studies. All but one study included anti-synthetase autoantibody (ARS) positivity in the ASSD criteria. Most studies required only one ASSD feature plus anti-ARS to define ASSD (n=64, 78%), whereas 16 studies required more than one ASSD variable plus anti-ARS. The only criteria not including anti-ARS positivity required 5 ASSD clinical features. We found limited data and wide variability in the diagnostic performance of each variable and definition proposed in the literature. Given these limitations we only meta-analysed the performance of individual muscle biopsy and clinical variables in diagnosing ASSD, which performed poorly.
The current ASSD criteria include a variety of serological, clinical, and histological features with wide variability amongst proposed definitions and the performance of these definitions has not been tested. This systematic literature review suggests the need for additional data and consensus-driven classification criteria for ASSD.
PDF
