Comparison of clinical features between patients with anti-synthetase syndrome and dermatomyositis: Results from the MYONET registry.

OBJECTIVES: To compare clinical characteristics, including the frequency of cutaneous, extramuscular manifestations, and malignancy, between adults with anti-synthetase syndrome (ASyS) and dermatomyositis (DM). METHODS: Using data regarding adults from the MYONET registry, a cohort of DM patients with anti-Mi2/-TIF1É£/-NXP2/-SAE/-MDA5 autoantibodies, and a cohort of ASyS patients with anti-tRNA synthetase autoantibodies (anti-Jo1/-PL7/-PL12/-OJ/-EJ/-Zo/-KS) were identified. Patients with DM sine dermatitis or with discordant dual autoantibody specificities were excluded. Sub-cohorts of patients with ASyS with or without skin involvement were defined based on presence of DM-type rashes (heliotrope rash, Gottron's papules/sign, violaceous rash, shawl sign, V sign, erythroderma, and/or periorbital rash). RESULTS: In total 1,054 patients were included (DM, n = 405; ASyS, n = 649). In ASyS cohort, 31% (n = 203) had DM-type skin involvement (ASyS-DMskin). A higher frequency of extramuscular manifestations, including Mechanic's hands, Raynaud's phenomenon, arthritis, interstitial lung disease, and cardiac involvement differentiated ASyS-DMskin from DM (all p< 0.001), whereas higher frequency of any of four DM-type rashes: heliotrope rash (n = 248, 61% vs n = 90, 44%), violaceous rash (n = 166, 41% vs n = 57, 9%), V sign (n = 124, 31% vs n = 28, 4%), and shawl sign (n = 133, 33% vs n = 18, 3%) differentiated DM from ASyS-DMskin (all p< 0.005). Cancer-associated myositis (CAM) was more frequent in DM (n = 67, 17%) compared with ASyS (n = 21, 3%) and ASyS-DMskin (n = 7, 3%) cohorts (both p< 0.001). CONCLUSION: DM-type rashes are frequent in patients with ASyS; however, distinct clinical manifestations differentiate these patients from classical DM. Skin involvement in ASyS does not necessitate increased malignancy surveillance. These findings will inform future ASyS classification criteria and patient management.

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.

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.

Season Dependent Changes in the Expression of Protein Kinase C Isoenzymes in a Female Patient with Systemic Lupus Erythematosus.

We aimed to answer the question whether the decreased expression of protein kinase C (PKC) isoenzymes in the peripheral blood mononuclear cells (PBMC) of patients with systemic lupus erythematosus (SLE) is inherited or not. For this reason we examined the expression of PKC isoenzymes in a European white girl with acute SLE and in her healthy mother and father simultaneously in summer and winter during one year using western blotting and densitometry. We found that in the father the expression of PKC isoenzymes did not differ from that of eight healthy controls included women and men. However, in the "SLE-free" mother and in the patient arrived in July with acute symptoms of lupus, the expression of PKC isoenzymes showed a season dependent undulation in parallel. Namely, in summer the expression values were significantly lower, in winter they were significantly higher than those in the controls. Thus, the decreased expression of PKC isoenzymes in the PBMC of SLE patient is not a disease specific marker; it appears also in her lupus free mother. This phenomenon may be due to a season dependent female genetic background. However, the low PKC levels in summer can still decrease further the low production of IL-2 in T cells of lupus patients augmenting the existing AP-1 defects. This is the first report on the season and female dependent inherited changing of PKC expression in a European white patient with SLE and her mother. Further studies are needed to confirm these findings in other populations.

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.

[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.

[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.

[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.

[Severe necrotising primary vasculitis--case report]. / Súlyos nekrotizáló primer vasculitis.

INTRODUCTION: Vasculitis is an inflammatory disorder of the vessels, often associates with necrosis. The primary (idiopathic) form caused by distinct immunological mechanisms, the secondary form caused by infection, tumor, drugs or systemic autoimmune disease. CASE REPORT: 57-year-old smoking female patient with a medical history of the left ankle fracture. Four days earlier had sore throat, at admission was febrile and generally weak and had severe pain in her lower extremities. Physical examination revealed numerous livid alterations in both lower extremities, necrotic change of some toes and new onset of diastolic hypertension. Elevated serum transaminase levels, severe thrombopenia, anemia, leukocytosis suggested the possibility of thrombotic thrombocytopenic purpura and vasculitis. Tests ruled out septic embolism, therefore we applied high dose steroid treatment and plasma exchange. Meanwhile the results fulfilled the classification criteria of polyarteritis nodosa (vasculitis, livedo reticularis, polyneuropathia and new onset of diastolic hypertension), accordingly we synchronized the treatment with fractionally administered intravenous cyclophosphamide. The process revealed responsive to therapy and the substantive function of the legs remained after surgical removal of the necrotic areas. CONCLUSIONS: Early rapid diagnosis of vasculitis is fundamental and we emphasize the significance of the efficient treatment.