Melinda Nagy-Vincze

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.

Pregnancy outcome in idiopathic inflammatory myopathy patients in a multicenter study.

To the Editor: Pregnancy in autoimmune diseases may be complicated for both the fetus and the mother. Polymyositis (PM) and dermatomyositis (DM) are autoimmune diseases that affect women more often than men, and can occur before childbearing years1,2. Complications during pregnancy were frequently reported in patients with PM/DM with active disease, whereas there seems to be a low risk for the fetus and mother in women with a well-controlled disease at time of conception2,3,4,5,6,7,8,9,10. Our aims were to assess the pregnancy outcome in myositis. Based on international collaboration, records for women with PM/DM who had been pregnant after the diagnosis of myositis were searched in 4 countries using the clinical databases of contributing hospitals. There were 23 women identified: Czech Republic (n = 8), Hungary (n = 9), Sweden (n = 5), and Poland (n = 1). All 23 women were white. Medical records were retrospectively reviewed using a standardized protocol. Normal delivery was defined when a healthy newborn weighing > 2500 g was delivered after 37 weeks of pregnancy. Premature delivery was defined when the pregnancy … Address correspondence to Dr. M. Nagy-Vincze, Division of Clinical Immunology, Department of Internal Medicine, University of Debrecen, Moricz Zs. u. 22, H-4032 Debrecen, Hungary. E-mail: melinda.nagyvincze{at}gmail.com

[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.

Pharmacological management of dermatomyositis

ABSTRACT Introduction: Dermatomyositis is a rare heterogeneous systemic autoimmune disease with multiple organ involvement which can result in significant disability and mortality. Despite the lack of placebo-controlled trials, glucocorticoids are considered to be the mainstay of initial management. Treatment strategies are mainly based on uncontrolled studies, evidence based guidelines for treatments do not exist. Areas covered: This review provides an overview of the currently available pharmacological treatments in the field of dermatomyositis including conventional immunosuppressants, biologics and topical agents. The role of antibodies in different treatment responses of dermatomyositis related clinicoserological syndromes is also discussed. A PubMed search was performed in order to find relevant literature for this review. Expert commentary: Early recognition and intervention is essential to ameliorate disease outcome. Determination of antibodies provide a useful key in diagnosis, clinical manifestations, malignancy, prognosis, and treatment response and may lead to wider acceptance of personalized medicine. Corticosteroids with adjunctive steroid-sparing immunosuppressive therapies are recommended to treat disease activity, prevent mortality, and reduce long-term disability. Combinations of second-line therapies or newer third-line therapies are used in severe, refractory, or corticosteroid-dependent diseases. Further research is required to assess the role of new therapies.

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.

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.

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.

Effect of Genetic and Laboratory Findings on Clinical Course of Antisynthetase Syndrome in a Hungarian Cohort

The aim of this study was to determine the clinical, serological, and genetic features of anti-Jo-1 positive antisynthetase patients followed by a Hungarian single centre to identify prognostic markers, which can predict disease phenotypes and disease progression. It was a retrospective study using clinical database of 49 anti-Jo-1 positive patients. 100% of patients exhibited myositis, 73% interstitial lung disease, 88% arthritis, 65% Raynauds phenomenon, 43% fever, 33% mechanics hand, and 12% dysphagia. We could detect significant correlation between anti-Jo-1 titer and the CK and CRP levels at disease onset and during disease course. HLA DRB1⁎03 positivity was present in 68.96% of patients, where the CK level at diagnosis was significantly lower compared to the HLA DRB1⁎03 negative patients. HLA DQA1⁎0501-DQB1⁎0201 haplotype was found in 58.62% of patients, but no significant correlation was found regarding any clinical or laboratory features. Higher CRP, ESR level, RF positivity, and the presence of fever or vasculitic skin lesions at the time of diagnosis indicated a higher steroid demand and the administration of higher number of immunosuppressants during the follow-up within anti-Jo-1 positive patients. The organ involvement of the disease was not different in HLA-DRB1⁎0301 positive or negative patients who were positive to the anti-Jo-1 antibody; however, initial CK level was lower in HLA-DRB1⁎0301 positive patients. Distinct laboratory and clinical parameters at diagnosis could be considered as prognostic markers.