Levente Bodoki

Four dermatomyositis-specific autoantibodies—anti-TIF1γ, anti-NXP2, anti-SAE and anti-MDA5—in adult and juvenile patients with idiopathic inflammatory myopathies in a Hungarian cohort

Idiopathic inflammatory myopathies (IIMs) are chronic systemic autoimmune diseases characterised by symmetrical, proximal muscle weakness. Dermatomyositis represents one subset of IIMs, in which skin rashes are present in addition to muscle weakness. Myositis-specific antibodies can only be detected in myositis, and they are directed against specific proteins found in the cytoplasm or in the nucleus of cells. With this case-based article, we introduce the recently detected anti-TIF1γ, anti-NXP2, anti-SAE and anti-MDA5 antibodies that form various clinical groups. These antibodies could be detected in patients with dermatomyositis. The myositis-specific autoantibodies of three hundred and thirty-seven Hungarian patients with IIM were detected. Retrospective analysis of the clinical findings has also been introduced by revision of the medical history. We had twelve patients with anti-TIF1γ positivity, four patients with anti-NXP2 positivity and four patients with anti-SAE positivity. We did not have any positive anti-MDA5 patients. The most relevant clinical findings were similar to those seen in previously published reports. Eleven of the twelve patients with anti-TIF1γ positivity had classical dermatomyositis. Three of the twelve anti-TIF1γ patients had cancer during the disease progression. This was two out of four for the anti-NXP2 subgroup and one in four for the anti-SAE subgroup. In two juvenile dermatomyositis cases, typical ulceration was seen in patients with anti-TIF1γ positivity. The frequency of pulmonary fibrosis during the disease progression was 2/12, 1/4 and 1/4 in anti-TIF1γ, anti-NXP2 and anti-SAE, respectively. Other extra-muscular manifestations, such as arthralgia, dysphagia, dysphonia and dyspnoea, were also detectable. The myositis subgroups determined by these myositis-specific autoantibodies differ from each other in their symptoms, prognosis and therapy responsiveness. Their detection is helpful for the preparation of an adequate treatment, but in daily diagnostic methods, these antibodies cannot be detected. By presenting our anti-TIF1γ, anti-NXP2 and anti-SAE cases, we would like to highlight the clinical role of these antibodies.

[Anti-NXP2-positive dermatomyositis associated with ulcerative colitis and celiac disease].

The authors discuss a rare case of a 25-year-old female patient having dermatomyositis associated with celiac disease and ulcerative colitis. The idiopathic inflammatory myopathies are systemic, chronic, immune-mediated diseases characterized by proximal, symmetrical muscle weakness. Many examples from the literature refer that celiac disease occurs more often in patients with myositis than in the general population, but its association with ulcerative colitis is a real rarity in the international literature.A szerzők az idiopathias inflammatorikus myopathia ritka, colitis ulcerosaval es coeliakiaval tarsult esetet mutatjak be egy altaluk kezelt, 25 eves dermatomyositises nőbeteg kortorteneten keresztul. Az idiopathias inflammatorikus myopathiak szisztemas, kronikus, immunmedialt megbetegedesek, amelyeket a proximalis vegtagizmok szimmetrikus gyengesege jellemez. Irodalmi peldak utalnak ra, hogy a coeliakia gyakrabban jelentkezik myositisben, mint az atlagpopulacioban. Colitis ulcerosaval valo asszociacioja azonban irodalmi ritkasagnak szamit. Orv. Hetil., 2014, 155(26), 1033–1038.

Vitamin D receptor gene polymorphisms and haplotypes in Hungarian patients with idiopathic inflammatory myopathy.

Idiopathic inflammatory myopathies are autoimmune diseases characterized by symmetrical proximal muscle weakness. Our aim was to identify a correlation between VDR polymorphisms or haplotypes and myositis. We studied VDR-BsmI, VDR-ApaI, VDR-TaqI, and VDR-FokI polymorphisms and haplotypes in 89 Hungarian poly-/dermatomyositis patients (69 females) and 93 controls (52 females). We did not obtain any significant differences for VDR-FokI, BsmI, ApaI, and TaqI genotypes and allele frequencies between patients with myositis and healthy individuals. There was no association of VDR polymorphisms with clinical manifestations and laboratory profiles in myositis patients. Men with myositis had a significantly different distribution of BB, Bb, and bb genotypes than female patients, control male individuals, and the entire control group. Distribution of TT, Tt, and tt genotypes was significantly different in males than in females in patient group. According to four-marker haplotype prevalence, frequencies of sixteen possible haplotypes showed significant differences between patient and control groups. The three most frequent haplotypes in patients were the fbAt, FBaT, and fbAT. Our findings may reveal that there is a significant association: Bb and Tt genotypes can be associated with myositis in the Hungarian population we studied. We underline the importance of our result in the estimated prevalence of four-marker haplotypes.

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.

Az anti-Jo-1-pozitív antiszintetáz szindróma jellegzetességei gondozott betegeink alapján

Absztrakt Bevezetes: Az idiopathias inflammatorikus myopathiak a proximalis vegtagizmok szimmetrikus gyengesegevel jellemezhető szisztemas autoimmun betegsegek. Az anti-Jo-1 antitest jelenlete jellegzetes klinikai tunetegyuttessel (myositis, arthritis, interstitialis tudőbetegseg, Raynaud-jelenseg, laz, mechanikus kez), az antiszintetaz-szindromaval tarsul. Celkitűzes: A Debreceni Egyetem, Klinikai Kozpont, Klinikai Immunologiai Tanszek altal gondozott anti-Jo-1-pozitiv betegek demografiai adatainak, klinikai tuneteinek, illetve az alkalmazott kezelesuknek a vizsgalata. Modszer: 49 anti-Jo-1-pozitiv beteg dokumentaciojanak retrospektiv vizsgalatat vegeztek. Eredmenyek: A demografiai es klinikai adatok nagymertekben hasonlitottak az irodalomban megtalalhato mas centrumok eredmenyeihez. Igazoltak, hogy az anti-Jo-1-titer korrelal a betegseg aktivitasat is jelző kreatinkinaz- es C-reaktiv-protein-szintekkel. Kimutattak, hogy a betegseg diagnozisakor mert bizonyos laboratoriumi eredmenyek (C-reaktiv protein, ...

Late onset dysferlinopathy mimicking treatment resistant polymyositis

Joint Bone Spine - In Press.Proof corrected by the author Available online since mardi 13 octobre 2015

[Comparison of clinical characteristics and laboratory parameters of patients with dermatomyositis-specific autoantibodies and autoantibody-negative patients].

INTRODUCTION Myositis is an autoimmune disease characterised by proximal muscle weakness. AIM The aim of the authors was to determine the frequency of dermatomyositis-specific autoantibodies (anti-Mi-2, anti-transcriptional intermediary factor 1 gamma, anti-nuclear matrix protein 2, anti-small ubiquitin-like modifier activating enzyme, anti-melanoma differentiation-associated gene) in a Hungarian myositis population and to compare the clinical features with the characteristics of patients without myositis-specific antibodies. METHOD Antibodies were detected using immunoblot and immunoprecipitation. RESULTS Of the 330 patients with myositis, 48 patients showed dermatomyositis-specific antibody positivity. The frequency of antibodies in these patients was lower than those published in literature Retrospective analysis of clinical findings and medical history revealed that patients with dermatomyositis-specific autoantibody had more severe muscle weakness and severe skin lesions at the beginning of the disease. CONCLUSIONS Antibodies seem to be useful markers for distinct clinical subsets, for predicting the prognosis of myositis and the effectiveness of the therapy.

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.

Risk factors for cancer in patients with myositis. Clinical, immunological characteristics and the role of the anti-p155/140 antibody

INTRODUCTION Idiopathic inflammatory myopathies are systemic autoimmune diseases characterized by progressive proximal muscle weakness. Cancer-associated myositis represents the worst prognostic group within this heterogeneous disease. AIM The aim of this study was to reveal factors which increase the risk factors for association of cancerous disease in patients with myositis. Furthermore, the authors explored the most common types of associated malignancies in their patients with myositis and characterize the clinical findings in a sub-group of anti-p155/140 positive patients. METHOD In this retrospective study, myositis patients with and without associated cancer were analysed (32 and 64 patients, respectively). In addition, anti-p155/140 positive and negative groups were compared, irrespective to the presence of associated malignancies. RESULTS The risk for associated malignancy was higher in patients with severe muscle and skin symptoms and those with dermatomyositis. Furthermore, increased risk for malignancy was noted in the presence of particular skin symptoms and the absence of systemic symptoms. The anti-p155/140 antibody was proved to be a feasible marker of an independent clinical sub-group which overlapped clinical characteristics with cancer-associated myositis. CONCLUSIONS These results may help the identification of patients with myositis with a higher risk for associated malignancy.Idiopathic inflammatory myopathies are systemic autoimmune diseases characterized by progressive proximal muscle weakness. Cancer-associated myositis represents the worst prognostic group within this heterogeneous disease. Aim: The aim of this study was to reveal factors which increase the risk factors for association of cancerous disease in patients with myositis. Furthermore, the authors explored the most common types of associated malignancies in their patients with myositis and characterize the clinical findings in a sub-group of anti-p155/140 positive patients. Method: In this retrospective study, myositis patients with and without associated cancer were analysed (32 and 64 patients, respectively). In addition, anti-p155/140 positive and negative groups were compared, irrespective to the presence of associated malignancies. Results: The risk for associated malignancy was higher in patients with severe muscle and skin symptoms and those with dermatomyositis. Furthermore, increased risk for malignancy was noted in the presence of particular skin symptoms and the absence of systemic symptoms. The anti-p155/140 antibody was proved to be a feasible marker of an independent clinical sub-group which overlapped clinical characteristics with cancer-associated myositis. Conclusions: These results may help the identification of patients with myositis with a higher risk for associated malignancy. Orv. Hetil., 2014, 155(36), 1437–1444.

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.