Melinda Vincze

Anti-PL-7 (Anti-Threonyl-tRNA synthetase) Antisynthetase syndrome: Clinical manifestations in a series of patients from a european multicenter study (EUMYONET) and review of the literature

AbstractAutoantibodies against several aminoacyl-transfer-RNA synthetases have been described in patients with myositis; anti-threonyl-tRNA synthetase (anti-PL-7) is one of the rarest. We describe the clinical and laboratory characteristics of a cohort of European anti-PL-7 patients, and compare them with previously reported cases. This multicenter study of patients positive for anti-PL-7, identified between 1984 and 2011, derives from the EUMYONET cohort. Clinical and serologic data were obtained by retrospective laboratory and medical record review, and statistical analyses were performed with chi-squared and Fisher exact tests.Eighteen patients, 15 women, were anti-PL-7 antibody positive. Median follow-up was 5.25 years (interquartile range, 2.8–10.7 yr), and 4 patients died. All patients had myositis (12 polymyositis, 5 dermatomyositis, and 1 amyopathic dermatomyositis), 10 (55.6%) had interstitial lung disease, and 9 (50%) had pericardial effusion. Occupational exposure to organic/inorganic particles was more frequent in patients with interstitial lung disease than in the remaining patients (5 of 10 vs. 1 of 7; p = 0.152), although the difference was not significant. Concurrent autoantibodies against Ro60 and Ro52 were seen in 8 of 14 (57%) patients studied. In the literature review the most common manifestations of anti-PL-7 antisynthetase syndrome were interstitial lung disease (77%), myositis (75%), and arthritis (56%). As in other subsets of the antisynthetase syndrome, myositis and interstitial lung disease are common features of the anti-PL-7 antisynthetase syndrome. In addition, we can add pericarditis as a possible manifestation related to anti-PL-7 antibodies.

Interaction of HLA-DRB1*03 and smoking for the development of anti-Jo-1 antibodies in adult idiopathic inflammatory myopathies: a European-wide case study

Objectives HLA-DRB1*03 is strongly associated with anti-Jo-1-positive idiopathic inflammatory myopathies (IIM) and there is now increasing evidence that Jo-1 antigen is preferentially expressed in lung tissue. This study examined whether smoking was associated with the development of anti-Jo-1 antibodies in HLA-DRB1*03-positive IIM. Methods IIM cases were selected with concurrent information regarding HLA-DRB1 status, smoking history and anti-Jo-1 antibody status. DNA was genotyped at DRB1 using a commercial sequence-specific oligonucleotide kit. Anti-Jo-1 antibody status was established using a line blot assay or immunoprecipitation. Results 557 Caucasian IIM patients were recruited from Hungary (181), UK (99), Sweden (94) and Czech Republic (183). Smoking frequency was increased in anti-Jo-1-positive IIM cases, and reached statistical significance in Hungarian IIM (45% Jo-1-positive vs 17% Jo-1-negative, OR 3.94, 95% CI 1.53 to 9.89, p<0.0001). A strong association between HLA-DRB1*03 and anti-Jo-1 status was observed across all four cohorts (DRB1*03 frequency: 74% Jo-1-positive vs 35% Jo-1-negative, OR 5.55, 95% CI 3.42 to 9.14, p<0.0001). The frequency of HLA-DRB1*03 was increased in smokers. The frequency of anti-Jo-1 was increased in DRB1*03-positive smokers vs DRB1*03-negative non-smokers (42% vs 8%, OR 7.75, 95% CI 4.21 to 14.28, p<0.0001) and DRB1*03-positive non-smokers (42% vs 31%, p=0.08). In DRB1*03-negative patients, anti-Jo-1 status between smokers and non-smokers was not significantly different. No significant interaction was noted between smoking and DRB1*03 status using anti-Jo-1 as the outcome measure. Conclusion Smoking appears to be associated with an increased risk of possession of anti-Jo-1 in HLA-DRB1*03-positive IIM cases. The authors hypothesise that an interaction between HLA-DRB1*03 and smoking may prime the development of anti-Jo-1 antibodies.

Primary lung adenocarcinoma associated with anti-Jo-1 positive polymyositis

We present a female with anti-Jo-1 positive polymyositis and lung adenocarcinoma. Her polymyositis diagnosis was based on her clinical symptoms, electromyography results, and highly elevated muscle enzymes, including creatine kinase and lactate-dehydrogenase. Anti-Jo-1 positivity, leukocytosis and elevated tumor markers: CA 15-3 and CA 72-4 were also certified at the diagnosis. Her malignancy was finally diagnosed by transthoracic needle biopsy, two years after the appearance of first symptoms of polymyositis. After surgical removal of the tumor, polymyositis was in remission. Due to the symptoms mentioned above and the coincidence of the tumor, a paraneoplastic myositis was suspected.

New therapeutic approaches for polymyositis and dermatomyositis

Inflammatory myopathies are chronic, immune-mediated diseases characterized with progressive proximal muscle weakness. They encompass a variety of syndromes with protean manifestations. The aims of therapy are to increase muscle strength, prevent the development of contractures, and to manage the systemic manifestations of the disease. This is a complex treatment which requires routine and wide knowledge. The most important task is to recognize the disease and guide the patient to immunologic center. Although the first line of therapy continues to include corticosteroids, there are a multitude of agents available for treating patients with myositis. There are several different immunosuppressive agents which may be applied alone or in combination with each other, as well as an increasing number of novel and exciting biologic agents targeting molecules participating in the pathogenesis of inflammatory myopathy. Physiotherapy and rehabilitation in the remission period may significantly improve the functional outcome of patients with these disorders.

Inclusion body myositis — a case based clinicopathological update

Inclusion body myositis is a slowly progressive myopathy affecting predominantly the middle-aged and older patient population. It is a major form of the idiopathic inflammatory myopathies which are chronic systemic autoimmune diseases characterized by symmetrical proximal muscle weakness. Unfortunately, there is no effective therapy yet; however, the early diagnosis is essential to provide treatment options which may significantly slow the progression of the disease. In our case-based clinicopathological study the importance of the close collaboration between the clinician and the neuropathologist is emphasised.

Inclusion body myositis – pathomechanism and lessons from genetics

Abstract Inclusion body myositis is a rare, late-onset myopathy. Both inflammatory and myodegenerative features play an important role in their pathogenesis. Overlapping clinicopathological entities are the familial inclusion body myopathies with or without dementia. These myopathies share several clinical and pathological features with the sporadic inflammatory disease. Therefore, better understanding of the genetic basis and pathomechanism of these rare familial cases may advance our knowledge and enable more effective treatment options in sporadic IBM, which is currently considered a relentlessly progressive incurable disease.

SAT0207 Epidemiological Data of Patients with Idiopathic Inflammatory Myopathy from a Hungarian Myositis Centre

Background The idiopathic inflammatory myopathies (IIM) are systemic autoimmune disease characterised with proximal muscle weakness. The epidemiology of these multifactorial diseases is partially known. These are rare diseases and Immunological or Rheumatological centres or international collaborations are required to carry the majority or all of these patients. Nowadays there are studies for establishing national or international registry of IIM patient. The Myositis study group of Division of Clinical Immunology, Institution of Internal Medicine, University of Debrecen Medical and Health Science Centre have been found in 1975. Most of the Hungarian patients are carried in this department since then. So we have preliminary epidemiological data of Hungarian IIM patients. The database is under continuous development. Objectives The aim of this report is to show our epidemiological findings. Sex and age were analysed in each IIM subgroup. Standardized incidence rates were calculated as new cases/million population/year with 95% confidence interval (CI). Results Between 1999 and 2010 1119 patients were hospitalized due to IIM in Hungary. We selected the data of these years because we have less information about the patients before 1999 (no computerized data before this date). 288 patients were carried in our department. 61,93% suffered from polymyositis (PM), 32,17 % had dermatomyositis (DM), 4,15% had juvenile dermatomyositis (JDM), 0,69% was diagnosed with amyopathic dermatomyositis (ADM) and we found other myositis (OTM) in 1,03% of the patients. The mean age of patients was 47,73 years (ys), respectively 48,46 ys (PM) – 52,19 ys (DM) -9,66 ys (JDM) – 34 ys (ADM) – 32 ys (OTM) in the subgroups. 67,82% of the patients were adult woman (mean age: 50,07 ys), we found 27,68 % of adult man (mean age:49,11 ys) and 4,5% children (9,6 ys). Cancer associated myositis was found in 31 cases (10,72%), the mean age of patients were 53,51 years. The most frequent tumor types were breast and lung cancer but gastrointestinal, reproductive and hematological malignancies were also presented. Overlap syndromes, preciously the association of IIM with other autoimmune diseases have been found in 14 cases (4,84%), the mean age of these patients were 44,64 years. The mainly presented overlap syndrome was Systhemic sclerosis and Sjögren’s syndrome. The average incidence rate was 0.95 cases per 100.000 persons per year. Conclusions Our results represented that the epidemiological data of Hungarian IIM population correlate with the former publicised findings. IIM commonly developed in middle-aged woman. The male/female ratio is 1/2. Dermatomyositis can occur in children and in adults as well, however PM is mainly the disease of adults. These are rare diseases with incidence of 0.1-1 /100.000/year. Our next goal is to develop a National Registry for IIM patients to have more information about epidemiological, clinical and serological characteristics of Hungarian patients. Disclosure of Interest None Declared

THU0253 ANTI-PM-SCL autoantibodies in polymyositis and dermatomyositis

Background Idiopathic inflammatory myopathies (IIM) are frequently accompanied by presence of autoantibodies. A correlation of anti-Jo-1 and anti-SRP antibody levels with disease activity and creatine kinase levels has been described. Recently a new anti-PM1α quantitative ELISA test detecting antibodies to the main epitope of PM-Scl-100 has become available. Objectives To investigate the prevalence of anti-PM1α autoantibodies and association with clinical symptoms, clinical disease activity and serum CK in a multicenter myositis cohort. Methods Two hundred and thirty eight consecutive patients with established IIM (103 DM, 99 PM, 8 JDM, 3 IBM and 25 IIM/CTD-overlap syndrome) were tested for the presence of anti PM-Scl autoantibodies by immunoblot and by immunoprecipitation. Eight additional anti-PM-Scl positive sera were also obtained. Serum levels of anti-PM1α autoantibodies were detected by ELISA kit (Dr. FOOKE Laboratorien GmbH, Neuss, DE). Clinical data were derived from the Euromyositis database (www.euromyositis.eu). Global and organ clinical disease activities were assessed by Myositis Activity Assessment Tool (MYOACT) 10 cm visual analogue scales. Results 19/238 (8%) patients (11 DM, 2 PM and 6 IIM/CTD-overlap syndrome (3 DM + SSc, 2 PM + SSc, 1 PM + SjS)) were positive for anti-PM-Scl in immunoblot, immunoprecipitation and anti-PM1α ELISA. 19 PM-Scl+ were 16/181 women and 3/57 men, average age 50.5 years (22.0 – 74.2) and average disease duration 3.0 years (0 – 11.6 years). Good agreement between detection tests was found. The most common clinical features among anti-PM-Scl positive patients were muscle weakness (96%), interstitial lung disease (77%), Raynaud’s phenomenon (69%) and mechanic’s hands (65%). One patient had a cancer. Anti-PM1α levels correlated with serum CK activity in the DM group (p=0.041, r=0.533) and with constitutional disease activity and seriousness of dysphagia in the PM group (p=0.048, r=0.768 and p=0.007, r=0.927). Furthermore longitudinal change in anti-PM1α levels correlated with HAQ scores in the whole group (p=0.016, r=0.730) and with global disease activity score in DM group (p=0.023, r=0.685), but not with other MYOACT parameters. Conclusions Anti-PM-Scl autoantibodies are detected in 8% of patients with myositis. They are more frequent in those with DM and overlap syndromes. Presence of these autoantibodies is associated with muscle weakness, ILD, Raynaud’s phenomenon and mechanic’s hands. Anti-PM1α levels correlate with serum CK levels in DM and their change is correlated with change of HAQ scores in the whole group and with MYOACT scores in DM group. This suggests that the quantitative measurement of anti-PM-1α may be a useful tool in the assessment of patients with this syndrome. Disclosure of Interest None Declared

Necrotizing autoimmune myopathy

Idiopathic inflammatory myopathies are systemic autoimmune diseases characterized by symmetrical proximal muscle weakness. One of them is the subgroup of necrotizing autoimmune myopathy, which has recently been recognized as a separate entity. In addition to the typical symmetrical muscle weakness, it is characterized by very high creatine kinase levels, myopathic triad in the electromyography, and myocyte necrosis without significant inflammation. The paper aims to review this rare entity, which has to be diagnosed and treated quickly in every case.

Intravenous immunoglobulin treatment in idiopathic inflammatory myopathy

Idiopathic inflammatory myopathies are chronic, systemic autoimmune diseases, characterized by symmetric and progressive weakness of proximal muscles in the upper and lower extremities. Treatment of the disease presents a complex challenge and it needs practical knowledge. In this review the authors summarize current treatment options, and discuss intravenous immunoglobulin treatment in therapy-unresponsive cases. Relevant data from the international literature is collected, too. Benefits and side effects of this treatment are also disclosed.