Pruritogenic molecules in the skin of patients with dermatomyositis.

Introduction: Pruritus is a common excruciating symptom in systemic autoimmune diseases such as dermatomyositis (DM) but the pathogenesis is not fully understood. We intended to investigate the targeted expression analysis of candidate molecules involved in the development of pruritus in lesional vs. non-lesional skin samples of patients affected with active DM. We looked for correlations between the investigated pruriceptive signaling molecules, disease activity, and itching sensation of DM patients. Methods: Interleukins (IL-33 and IL-6), tumor necrosis factor α (TNF-α), peroxisome proliferator-activated receptor γ (PPAR-γ), and ion channels belonging to the transient receptor potential (TRP) family were analyzed. The expression of TNF-α, PPAR-γ, IL-33, IL-6, and TRP channels in lesional DM skin was evaluated by RT-qPCR and immunohistochemistry and was compared with non-lesional DM skin samples. Pruritus, disease activity, and damage of DM were evaluated by the 5-D itch scale and Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), respectively. Statistical analysis was performed with IBM SPSS 28 software. Results: A total of 17 active DM patients participated in the study. We could show that the itching score was positively correlated with the CDASI activity score (Kendall's tau-b = 0.571; p = 0.003). TNF-α gene expression was significantly higher in lesional DM skin than in non-lesional DM skin (p = 0.009) and differed in the subgroups of patients with different itch intensities (p = 0.038). The mRNA expression of lesional IL-6 correlated positively with 5-D itch and CDASI activity score (Kendall's tau-b = 0.585; p = 0.008 and 0.45; p = 0.013, respectively). TRPV4 expressions were positively correlated with CDASI damage score (Kendall's tau-b = 0.626; p < 0.001), but the mRNA expressions of the TRP family, PPAR-γ, IL-6, and IL-33 were not different in lesional and non-lesional samples. Immunohistochemistry analysis did not find significant alterations in the expressions of TNF-α, PPAR-γ, IL-6, and IL-33 in lesional and non-lesional regions. Discussion: Our results argue that cutaneous disease activity, TNF-α, and IL-6 might play a central role in DM-associated itch, while TRPV4 plays a central role in tissue regeneration.

Subclinical systolic and diastolic myocardial dysfunction in polyphasic polymyositis/dermatomyositis: a 2-year longitudinal study.

BACKGROUND: Cardiac involvement in patients with idiopathic inflammatory myopathies (IIM) is associated with increased morbidity and mortality risk; however, little is known about the progression of cardiac dysfunction and long-term data are scarce. In the present work, we intended to prospectively study echocardiographic parameters in patients with IIM for 2 years. METHODS: Twenty-eight IIM patients (41.9±1.6 years) without cardiovascular symptoms were enrolled. Patients with monophasic/polyphasic disease patterns were studied separately and compared to age-matched healthy individuals. Conventional echocardiographic and tissue Doppler imaging (TDI) parameters of systolic [LV: ejection fraction (EF), mitral annulus systolic movement (MAPSE), lateral s') and diastolic left (mitral inflow velocities, lateral anulus velocities: e', a', E/e') and right ventricular function (fractional area change: FAC, tricuspid annulus plane systolic excursion: TAPSE) were measured at the time of the diagnosis and 2 years later. RESULTS: Subclinical LV systolic dysfunction is characterized by reduced lateral s' (10.4 vs. 6.4 cm/s, p<0.05), EF (62.6±0.6%, vs. 51.7±0.7%) and MAPSE (18.5±0.6 vs. 14.5±0.6 mm) could be observed in IIM patients with polyphasic disease course 2 years after diagnosis compared to controls. Furthermore, diastolic LV function showed a marked deterioration to grade I diastolic dysfunction at 2 years in the polyphasic group (lateral e': 12.9 ±0.6, vs. 7.4±0.3 cm/s; lateral a': 10.7±0.3, vs. 17.3±0.8 cm/s; p<0.05) supported by larger left atrium (32.1±0.6 vs. 37.8±0.6 mm; p<0.05]. TDI measurements confirmed subclinical RV systolic dysfunction in polyphasic patients 2 years after diagnosis (FAC: 45.6±1.8%, vs. 32.7±1.4%; TAPSE: 22.7±0.5, vs. 18.1±0.3 mm; p<0.05). Similar, but not significant tendencies could be detected in patients with monophasic disease patterns. Polyphasic patients showed significantly (p<0.05) worse results compared to monophasic patients regarding EF (51.7±0.7% vs. 58.1±0.6%), lateral s' (6.4±0.4 cm/sec vs. 8.6±0.4 cm/s,), left atrium (37.8±0.6 mm vs. 33.3±0.8 mm), FAC (32.7±1.4% vs. 41.0±1.6%) and TAPSE (18.1±0.3 mm vs. 21.3±0.7 mm). CONCLUSIONS: Significant subclinical cardiac dysfunction could be detected in IIM patients with polyphasic disease course 2 years after diagnosis, which identifies them as a high-risk population. TDI is a useful method to detect echocardiographic abnormalities in IIM complementing conventional echocardiography and can recognize the high cardiac risk.

Heme-Induced Oxidation of Cysteine Groups of Myofilament Proteins Leads to Contractile Dysfunction of Permeabilized Human Skeletal Muscle Fibres.

Heme released from red blood cells targets a number of cell components including the cytoskeleton. The purpose of the present study was to determine the impact of free heme (20-300 µM) on human skeletal muscle fibres made available during orthopedic surgery. Isometric force production and oxidative protein modifications were monitored in permeabilized skeletal muscle fibre segments. A single heme exposure (20 µM) to muscle fibres decreased Ca2+-activated maximal (active) force (Fo) by about 50% and evoked an approximately 3-fold increase in Ca2+-independent (passive) force (Fpassive). Oxidation of sulfhydryl (SH) groups was detected in structural proteins (e.g., nebulin, α-actinin, meromyosin 2) and in contractile proteins (e.g., myosin heavy chain and myosin-binding protein C) as well as in titin in the presence of 300 µM heme. This SH oxidation was not reversed by dithiothreitol (50 mM). Sulfenic acid (SOH) formation was also detected in the structural proteins (nebulin, α-actinin, meromyosin). Heme effects on SH oxidation and SOH formation were prevented by hemopexin (Hpx) and α1-microglobulin (A1M). These data suggest that free heme has a significant impact on human skeletal muscle fibres, whereby oxidative alterations in structural and contractile proteins limit contractile function. This may explain and or contribute to the weakness and increase of skeletal muscle stiffness in chronic heart failure, rhabdomyolysis, and other hemolytic diseases. Therefore, therapeutic use of Hpx and A1M supplementation might be effective in preventing heme-induced skeletal muscle alterations.

Eight pillars of oncorheumatology: Crossroads between malignancies and musculoskeletal diseases.

ONCORHEUMATOLOGY: RELATIONSHIP BETWEEN MALIGNANCIES AND MUSCULOSKELETAL DISEASES: Oncorheumatology is the meeting point of tumor formation and rheumatic musculoskeletal diseases (RMD). Multiple interactions exist between these two medical specialties. One major field is the topic of malignancies associated with rheumatic diseases, while the other topic covers the development of musculoskeletal disease in cancer patients. Within the first group, secondary malignancies may be associated with rheumatic diseases. Mostly sustained inflammation is responsible for transition into cancer. Tumor-associated antigens (TAA) with adhesive properties are present on tumor cells. These molecules may also be expressed by inflammatory leukocytes and soluble TAA levels may be elevated in RMDs. There has been continuous debate with respect to the possible carcinogenicity of conventional and targeted antirheumatic drugs. Very recent data from registries suggest that neither biologics, nor JAK inhibitors increase cancer risk in arthritis patients. The issue of physiotherapy in rheumatic patients with recent or current cancer has also been controversial. Some modalities, primarily exercise, may be safely applied to patients with RMD and cancer. The second large topic includes paraneoplastic syndromes. Musculoskeletal paraneoplasias are triggered by tumor-derived mediators. These syndromes are sometimes slightly different from the classical RMDs. Various chemotherapies may also be associated with autoimmune side effects. Recently, these immune-related complications have also been observed in cancer patients treated with immune-checkpoint inhibitors. Sex hormone-deprivation therapies, such as aromatase inhibitors and anti-androgens are widely used for the treatment of breast and prostate cancer, respectively. These compounds may induce bone loss and lead to osteoporosis. Finally, primary and secondary malignancies of the musculoskeletal system may also interest rheumatologists. In this review, the clinical, practical aspects of these eight pillars of oncorheumatology will be discussed.

Oncorheumatology: relationship between malignancies and musculoskeletal diseases / Onkoreumatológia: a daganatos és mozgásszervi kórképek összefüggései

Oncorheumatology is the meeting point of tumour formation and rheumatic diseases. Multiple interactions exist between these two medical specialties. One major field is the topic of malignancies associated with rheumatic diseases, while the other topic covers the development of musculoskeletal disease in cancer patients. In the first group, secondary malignancies associated with rheumatic diseases, role of tumour-associated antigens in rheumatology, the possible carcinogenicity of conventional and targeted antirheumatic drugs and physical therapy of rheumatic patients with recent or current cancer will be discussed. The second large topic includes paraneoplastic syndromes, autoimmune-rheumatic side effects of oncotherapies (chemotherapy and immunotherapy), effects of hormone-deprivation therapies on bone and primary and secondary malignancies of the musculoskeletal system. Orv Hetil. 2020; 161(28): 1151-1165.

Retrospective Analysis of Cancer-Associated Myositis Patients over the Past 3 Decades in a Hungarian Myositis Cohort.

Association between cancer and myositis has been extensively reported and malignancy is a potentially life-threating complication in myositis. In this retrospective study authors give an overview of Hungarian cancer-associated myositis (CAM) patients treated at a single centre managing 450 myositis patients. All patients were diagnosed according to Bohan and Peter. Statistical analysis of disease onset, age, sex, muscle, skin and extramuscular symptoms, muscle enzymes, presence of antibodies, treatment and prognosis was performed. 43 patients could be considered as having CAM. 83.72% had cancer within one year of diagnosis of myositis. Most common localizations were ductal carcinoma of breast and adenocarcinoma of lung. Significant differences were observed between CAM and the non-CAM control patients: DM:PM ratio was 2.31:1 vs. 0.87:1, respectively (p = 0.029), age at diagnosis was 56.60 ± 12.79 vs. 38.88 ± 10.88 years, respectively (p < 0.001). Tumour-treatment was the following: surgical removal in 55.81%, chemotherapy in 51.1%, radiotherapy in 39.53%, hormone treatment in 18.6%, combination therapy in 51.16% of patients. Muscle enzyme levels of patients undergoing surgery were significantly reduced after intervention. 36 patients died (83.72%); 25 DM (83.33%) and 11 PM patients (84.62%); 5 years survival was 15.4% for PM and 27.5% for DM. This study demonstrates that DM, distal muscle weakness, asymmetric Raynaud's phenomenon, older age, ANA-negativity are risk factors for developing malignancy and polymyositis patients have less chance of long-lasting survival. It is very important to think about cancer and follow every single myositis patient in the clinical routine because survival rate of CAM is very poor.

Identification of a novel autoantigen eukaryotic initiation factor 3 associated with polymyositis.

OBJECTIVES: To describe the prevalence and clinical associations of autoantibodies to a novel autoantigen, eukaryotic initiation factor 3 (eIF3), detected in idiopathic inflammatory myositis. METHODS: Sera or plasma from 678 PM patients were analysed for autoantigen specificity by radio-labelled protein immunoprecipitation (IPP). Samples immunoprecipitating the same novel autoantigens were further analysed by indirect immunofluorescence and IPP using pre-depleted cell extracts. The autoantigen was identified through a combination of IPP and MALDI-TOF mass spectrometry, and confirmed using commercial antibodies and IPP-western blots. Additional samples from patients with DM (668), DM-overlap (80), PM-overlap (191), systemic sclerosis (150), systemic lupus erythematosus (200), Sjogren's syndrome (40), rheumatoid arthritis (50) and healthy controls (150) were serotyped by IPP as disease or healthy controls. RESULTS: IPP revealed a novel pattern in three PM patients (0.44%) that was not found in disease-specific or healthy control sera. Indirect immunofluorescence demonstrated a fine cytoplasmic speckled pattern for all positive patients. Mass spectrometry analysis of the protein complex identified the target autoantigen as eIF3, a cytoplasmic complex with a role in the initiation of translation. Findings were confirmed by IPP-Western blotting. The three anti-eIF3-positive patients had no history of malignancy or interstitial lung disease, and had a favourable response to treatment. CONCLUSION: We report a novel autoantibody in 0.44% of PM patients directed against a cytoplasmic complex of proteins identified as eIF3. Although our findings need further confirmation, anti-eIF3 appears to correlate with a good prognosis and a favourable response to treatment.

The EuroMyositis registry: an international collaborative tool to facilitate myositis research.

AIMS: The EuroMyositis Registry facilitates collaboration across the idiopathic inflammatory myopathy (IIM) research community. This inaugural report examines pooled Registry data. METHODS: Cross-sectional analysis of IIM cases from 11 countries was performed. Associations between clinical subtypes, extramuscular involvement, environmental exposures and medications were investigated. RESULTS: Of 3067 IIM cases, 69% were female. The most common IIM subtype was dermatomyositis (DM) (31%). Smoking was more frequent in connective tissue disease overlap cases (45%, OR 1.44, 95% CI 1.09 to 1.90, p=0.012). Smoking was associated with interstitial lung disease (ILD) (OR 1.32, 95% CI 1.06 to 1.65, p=0.013), dysphagia (OR 1.43, 95% CI 1.16 to 1.77, p=0.001), malignancy ever (OR 1.78, 95% CI 1.36 to 2.33, p<0.001) and cardiac involvement (OR 2.40, 95% CI 1.60 to 3.60, p<0.001).Dysphagia occurred in 39% and cardiac involvement in 9%; either occurrence was associated with higher Health Assessment Questionnaire (HAQ) scores (adjusted OR 1.79, 95% CI 1.43 to 2.23, p<0.001). HAQ scores were also higher in inclusion body myositis cases (adjusted OR 3.85, 95% CI 2.52 to 5.90, p<0.001). Malignancy (ever) occurred in 13%, most commonly in DM (20%, OR 2.06, 95% CI 1.65 to 2.57, p<0.001).ILD occurred in 30%, most frequently in antisynthetase syndrome (71%, OR 10.7, 95% CI 8.6 to 13.4, p<0.001). Rash characteristics differed between adult-onset and juvenile-onset DM cases ('V' sign: 56% DM vs 16% juvenile-DM, OR 0.16, 95% CI 0.07 to 0.36, p<0.001). Glucocorticoids were used in 98% of cases, methotrexate in 71% and azathioprine in 51%. CONCLUSION: This large multicentre cohort demonstrates the importance of extramuscular involvement in patients with IIM, its association with smoking and its influence on disease severity. Our findings emphasise that IIM is a multisystem inflammatory disease and will help inform prognosis and clinical management of patients.

2017 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Adult and Juvenile Idiopathic Inflammatory Myopathies and Their Major Subgroups.

OBJECTIVE: To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. METHODS: Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology, and pediatric clinics worldwide. Several statistical methods were utilized to derive the classification criteria. RESULTS: Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cutoff of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) "probable IIM," had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to "definite IIM." A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy), rules out IIM, leaving a probability of ≥50-<55% as "possible IIM." CONCLUSION: The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology, and pediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of "definite," "probable," and "possible" IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.

2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups.

OBJECTIVE: To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. METHODS: Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology and paediatric clinics worldwide. Several statistical methods were used to derive the classification criteria. RESULTS: Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cut-off of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) 'probable IIM', had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to 'definite IIM'. A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy), rules out IIM, leaving a probability of ≥50 to <55% as 'possible IIM'. CONCLUSIONS: The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology and paediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of 'definite', 'probable' and 'possible' IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.

Pharmacological management of dermatomyositis.

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.

Anti-HMGCR antibodies as a biomarker for immune-mediated necrotizing myopathies: A history of statins and experience from a large international multi-center study.

In an effort to find naturally occurring substances that reduce cholesterol by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), statins were first discovered by Endo in 1972. With the widespread prescription and use of statins to decrease morbidity from myocardial infarction and stroke, it was noted that approximately 5% of all statin users experienced muscle pain and weakness during treatment. In a smaller proportion of patients, the myopathy progressed to severe morbidity marked by proximal weakness and severe muscle wasting. Remarkably, Mammen and colleagues were the first to discover that the molecular target of statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), is an autoantibody target in patients that develop an immune-mediated necrotizing myopathy (IMNM). These observations have been confirmed in a number of studies but, until today, a multi-center, international study of IMNM, related idiopathic inflammatory myopathies (IIM), other auto-inflammatory conditions and controls has not been published. Accordingly, an international, multi-center study investigated the utility of anti-HMGCR antibodies in the diagnosis of statin-associated IMNM in comparison to different forms of IIM and controls. This study included samples from patients with different forms of IIM (n=1250) and patients with other diseases (n=656) that were collected from twelve sites and tested for anti-HMGCR antibodies by ELISA. This study confirmed that anti-HMGCR autoantibodies, when found in conjunction with statin use, characterize a subset of IIM who are older and have necrosis on muscle biopsy. Taken together, the data to date indicates that testing for anti-HMGCR antibodies is important in the differential diagnosis of IIM and might be considered for future classification criteria.

[Comparison of clinical characteristics and laboratory parameters of patients with dermatomyositis-specific autoantibodies and autoantibody-negative patients]. / Dermatomyositis-specifikus autoantitesttel rendelkezo és autoantitest-negatív betegeink klinikai jellemzoinek és laboratóriumi paramétereinek összehasonlítása.

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]. / Zárványtestes myositis.

The idiopathic inflammatory myopathies are systemic, chronic autoimmune diseases characterized by proximal symmetrical muscle weakness. One of the main diseases in this group is inclusion body myositis (IBM), an underdiagnosed, progressive muscle disease characteristically affecting the middle-aged and older population. It has a slow, relentlessly progressive course. The precise pathogenesis of the disease remains unknown. In most of the cases it is diagnosed a few years after the appearance of the first symptoms. The muscle biopsy typically shows endomysial inflammation, with invasion of mononuclear cells into the non-necrotic fibers, and also rimmed vacuoles. It appers, that both inflammation and degeneration are present at the onset of the disease. Our aim is to raise awareness about this disease which leads to severe disability, with clinicopathological case presentations and literature overview, emphasizing the importance of collaboration between the clinician and the neuropathologist. No effective therapy is currently available but the rapid diagnosis is essential to slow disease progression. Although this is a relatively rare disease, patients are presenting not only in immunology outpatient clinics; our reports aims to raise awareness and facilitate accurate early diagnosis of IBM.

HMGB1 expression and muscle regeneration in idiopathic inflammatory myopathies and degenerative joint diseases.

The High-Mobility Group Box 1 protein (HMGB1) is a known nuclear protein which may be released from the nucleus into the cytoplasm and the extracellular space. It is believed that the mobilized HMGB1 plays role in the autoimmune processes as an alarmin, stimulating the immune response. In addition, muscle regeneration and differentiation may also be altered in the inflammatory surroundings. Biopsy specimens derived from patients with idiopathic inflammatory myopathies (IIM) such as polymyositis or dermatomyositis were compared to muscle samples from patients undergoing surgical interventions for coxarthrosis. The biopsy and surgery specimens were used for Western blot analysis, for immunohistochemical detection of HMGB1 in histological preparations and for cell culturing to examine cell proliferation and differentiation. Our data show lower HMGB1 expression, impaired proliferation and slightly altered fusion capacity in the primary cell cultures started from IIM specimens than in cultures of coxarthrotic muscles. The ratio of regenerating muscle fibres with centralised nuclei (myotubes) is lower in the IIM samples than in the coxarthrotic ones but corticosteroid treatment shifts the ratio towards the coxarthrotic value. Our data suggest that the impaired regeneration capacity should also be considered to be behind the muscle weakness in IIM patients. The role of HMGB1 as a pathogenic signal requires further investigation.

[Anti-signal recognition particle autoantibody positive myopathy]. / Szignálfelismerorészecske-ellenes autoantitest-pozitív myopathia.

Idiopathic inflammatory myopathies are systemic, autoimmune diseases characterized by proximal symmetrical muscle weakness. We review the myositis-associated and myositis-specific autoantibodies, among them the anti-SRP autoantibody. Among those autoimmune myopathy cases, that are associated with autoantibodies, we can detect anti-SRP autoantibody positive myositis cases. We describe the role of signal recognition particle, its structure and role in protein biosynthesis. We review how necrotizing autoimmune myopathy is identified, and the differences from classical polymyositis. The anti-SRP titer correlates with disease activity. We present some cases to show how the disease appears in childhood and also some rare cases from the literature. Finally we present a case to draw attention to the importance of this disease.

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.

[Risk factors for cancer in patients with myositis. Clinical, immunological characteristics and the role of the anti-p155/140 antibody]. / Malignitás társulásának kockázatát fokozó tényezok vizsgálata myositises betegekben. Klinikai, immunológiai sajátosságok és az anti-p155/140 antitest szerepe.

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.

[Anti-NXP2-positive dermatomyositis associated with ulcerative colitis and celiac disease]. / Anti-NXP2-pozitív dermatomyositis társulása colitis ulcerosával és coeliakiával.

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.

[Biological therapy in idiopathic inflammatory myopathies]. / Biológiai terápia idiopathiás inflammatorikus myopathiákban.

Idiopathic inflammatory myopathies are systemic, immune-mediated diseases characterized by proximal, symmetrical, progressive muscle weakness. The aim of this work is to give an overview of the biological therapy used in the treatment of idiopathic inflammatory myopathies. The authors also focus on novel results in the therapy directed against the B- and T-cells. They emphasize the importance of new trials in these diseases which may lead to the introduction of novel therapeutic options in these disorders.