IDIOPATHIC INFLAMMATORY MYOPATHIES
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Idiopatické myozitidy či dysimunní myopatie a kolagenózy (difuzní onemocnění pojiva) mají v klinicko-patologickém obraze mnohé styčné body. Vyvstává otázka, zda a do jaké míry může bioptické vyšetření přispět ke stanovení diagnózy a diferenciální diagnózy těchto onemocnění. Termín dysimunní myopatie zahrnuje několik forem polymyozitidy (PM), dermatomyozitidy (DM) a myozitidy s přítomností inkluzních tělísek (IBM). V současné době nahlížíme na PM jako na celulárně (T-buňkami) zprostředkovanou imunitní myositis, na DM jako na protilátkově zprostředkovanou imunitní cévní poruchu a na IBM jako na degenerativní (metabolickou? infekční?) lézi se sekundárním zánětem. Základním znakem histopatologického obrazu bývá celulární reakce v interstitiu, tedy nález zánětlivého infiltrátu. Kromě toho může být cennou diagnostickou pomůckou i přítomnost MAC komplexu ve stěně krevních cév, přítomnost amyloidu v inkluzních tělíscích nebo exprese HLA 1. třídy v sarkolematické lokalizaci, ta však není pro myozitidy specifická. Kosterní sval může být postižen dystrofickými změnami i zánětem také u onemocnění, u nichž není hlavním terčem ataky, tedy zejména u kolagenóz. Patologické změny svalu u některých z těchto onemocnění mohou být stěží odlišitelné od idiopatických myozitid. Diferenciální diagnostiku v těchto případech usnadní klinické, biochemické a imunologické parametry. Aby biopsie mohla účinně přispět k diagnostice této skupiny onemocnění, je třeba vyšetřit typicky postižený sval nebo kožní excizi z míst s typickou morfou.
The clinical and pathologic picture of dysimmune or idiopathic myopathies and collagen-vascular diseases (connective tissue diseases) have many common features. Hence arose a question, whether and to what extent the bioptical examination may contribute to the correct diagnosis and differential diagnosis of these groups of diseases. The term dysimmune myopathies covers several forms of polymyositis, dermatomysitis and inclusion body myositis. Nowadays, polymyositis is considered a T cell mediated immune myositis, dermatomyositis a humoral mediated immune vascular lesion, while inclusion body myositis a degenerative (metabolic, infective?) lesion with a secondary inflammation. A characteristic feature of histopathological picture of myositis is cellular reaction, the presence of an inflammatory infiltration of the endo- and/or perimysium. Besides, the presence o MAC in the wall of small blood vessels, the presence of amyloid in the inclusions bodies and expression of HLA class I in the sarcolemma (not specific for the inflammatory myopathies) may be valuable diagnostic aid. Skeletal muscle may also be affected by inflammatory or dystrophic alterations in conditions in which it is not the primary target of the attack, particularly in collagen vascular diseases. Pathologic alterations of the skeletal muscle may be hardly distinguishable from idiopathic myositis. Differential diagnosis may be facilitated by the results of clinical, biochemical and immunological examination of the patient. In order to contribute to the diagnosis effectively, the biopsy must be taken from the typically affected muscle and/or from a typical lesion in the skin.
Diferenciální diagnostika idiopatických zánětlivých myopatií zahrnuje řadu stavů, které mohou způsobit svalovou slabost. V klasických případech dermatomyositidy není diagnóza obtížná, ale v případech polymyositidy, zejména se špatnou reakcí na imunosupresivní léčbu, je nutné vždy odlišit různá neurologická onemocnění, včetně svalových dystrofií, metabolické a endokrinní choroby, mitochondriální myopatie, infekce, stavy doprovázející maligní onemocnění, sarkoidózu a konečně i nežádoucí účinky léků, zejména statinů a fibrátů. Myositidy jsou většinou slušně léčitelné, především vyššími dávkami glukokortikoidů, často s přidáním imunosupresiv, jako jsou methotrexat, azathioprin, cyklosporin, případně cyklofosfamid.
A differential diagnosis of idiopathic inflammatory myopathies covers several situations, which may lead to muscle weakness. In the classical dermatomyositis case, the diagnosis is not difficult, however, in many polymyositis cases, particularly in those non-responsive to treatment, it is always necessary to differentiate several other diseases. These include neurological disorders, muscle dystrophies, metabolic and endocrine diseases, mitochondrial myopathies, malignant diseases, sarcoidosis and also adverse reactions to drug treatments, such as with statins or fibrates. Myositis is often amenable to treatment with the use of higher doses of glucocorticoids, frequently with addition of immunosuppressive drugs, such as methotrexate, azathioprine, cyclosporine or cyclophosphamide.
- MeSH
- dermatomyozitida diagnóza patologie terapie MeSH
- diferenciální diagnóza MeSH
- finanční podpora výzkumu jako téma MeSH
- hormony kůry nadledvin terapeutické užití MeSH
- imunosupresiva terapeutické užití MeSH
- lidé MeSH
- myozitida diagnóza patologie terapie MeSH
- polymyozitida diagnóza patologie terapie MeSH
- prospektivní studie MeSH
- svalová slabost diagnóza patologie terapie MeSH
- výsledek terapie MeSH
- zánět diagnóza patologie MeSH
- Check Tag
- lidé MeSH
The 255th ENMC workshop on Muscle Imaging in Idiopathic Inflammatory myopathies (IIM) aimed at defining recommendations concerning the applicability of muscle imaging in IIM. The workshop comprised of clinicians, researchers and people living with myositis. We aimed to achieve consensus on the following topics: a standardized protocol for the evaluation of muscle images in various types of IIMs; the exact parameters, anatomical localizations and magnetic resonance imaging (MRI) techniques; ultrasound as assessment tool in IIM; assessment methods; the pattern of muscle involvement in IIM subtypes; the application of MRI as biomarker in follow-up studies and clinical trials, and the place of MRI in the evaluation of swallowing difficulty and cardiac manifestations. The following recommendations were formulated: In patients with suspected IIM, muscle imaging is highly recommended to be part of the initial diagnostic workup and baseline assessment. MRI is the preferred imaging modality due to its sensitivity to both oedema and fat accumulation. Ultrasound may be used for suspected IBM. Repeat imaging should be considered if patients do not respond to treatment, if there is ongoing diagnostic uncertainty or there is clinical or laboratory evidence of disease relapse. Quantitative MRI is established as a sensitive biomarker in IBM and could be included as a primary or secondary outcome measure in early phase clinical trials, or as a secondary outcome measure in late phase clinical trials. Finally, a research agenda was drawn up.
- MeSH
- biologické markery MeSH
- kosterní svaly patologie MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- myozitida * diagnóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- konzilia MeSH
- Geografické názvy
- Nizozemsko MeSH
Major advances have been made in the field of idiopathic inflammatory myopathies (IIM), or myositis, that are likely to facilitate development of new therapeutic strategies that have not yet been applied in this group of diseases. These advances include new classification criteria to better identify the patients with IIM, detection of several new myositis-specific autoantibodies that facilitates subgrouping of patients into more specific clinical phenotypes, development of outcome measures for disease activity, and new response criteria. We have learned from clinical studies that exercise is an important part of treatment and that pharmacologic treatment should be combined with exercise.
- MeSH
- antirevmatika farmakologie MeSH
- autoprotilátky analýza MeSH
- lidé MeSH
- management péče o pacienta metody MeSH
- myozitida * diagnóza imunologie terapie MeSH
- stupeň závažnosti nemoci MeSH
- určení symptomu metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Idiopathic inflammatory myopathies (IIM), also known as myositis, are a heterogeneous group of autoimmune disorders with varying clinical manifestations, treatment responses and prognoses. Muscle weakness is usually the classical clinical manifestation but other organs can be affected, including the skin, joints, lungs, heart and gastrointestinal tract, and they can even result in the predominant manifestations, supporting that IIM are systemic inflammatory disorders. Different myositis-specific auto-antibodies have been identified and, on the basis of clinical, histopathological and serological features, IIM can be classified into several subgroups - dermatomyositis (including amyopathic dermatomyositis), antisynthetase syndrome, immune-mediated necrotizing myopathy, inclusion body myositis, polymyositis and overlap myositis. The prognoses, treatment responses and organ manifestations vary among these groups, implicating different pathophysiological mechanisms in each subtype. A deeper understanding of the molecular pathways underlying the pathogenesis and identifying the auto-antigens of the immune reactions in these subgroups is crucial to improving outcomes. New, more homogeneous subgroups defined by auto-antibodies may help define disease mechanisms and will also be important in future clinical trials for the development of targeted therapies and in identifying biomarkers to guide treatment decisions for the individual patient.
- MeSH
- autoimunitní nemoci * diagnóza MeSH
- autoprotilátky MeSH
- dermatomyozitida * patologie terapie MeSH
- lidé MeSH
- myozitida s inkluzními tělísky * patologie MeSH
- myozitida * diagnóza patologie MeSH
- svalová slabost MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Intramural MeSH
INTRODUCTION: The purpose of this study was to evaluate and compare the serum levels and local expression of resistin in patients with idiopathic inflammatory myopathies to controls, and to determine the relationship between resistin levels, inflammation and disease activity. METHODS: Serum resistin levels were determined in 42 patients with inflammatory myopathies and 27 healthy controls. The association among resistin levels, inflammation, global disease activity and muscle strength was examined. The expression of resistin in muscle tissues from patients with inflammatory myopathies and healthy controls was evaluated. Gene expression and protein release from resistin-stimulated muscle and mononuclear cells were assessed. RESULTS: In patients with inflammatory myopathies, the serum levels of resistin were significantly higher than those observed in controls (8.53 ± 6.84 vs. 4.54 ± 1.08 ng/ml, P < 0.0001) and correlated with C-reactive protein (CRP) levels (r = 0.328, P = 0.044) and myositis disease activity assessment visual analogue scales (MYOACT) (r = 0.382, P = 0.026). Stronger association was observed between the levels of serum resistin and CRP levels (r = 0.717, P = 0.037) as well as MYOACT (r = 0.798, P = 0.007), and there was a trend towards correlation between serum resistin and myoglobin levels (r = 0.650, P = 0.067) in anti-Jo-1 positive patients. Furthermore, in patients with dermatomyositis, serum resistin levels significantly correlated with MYOACT (r = 0.667, P = 0.001), creatine kinase (r = 0.739, P = 0.001) and myoglobin levels (r = 0.791, P = 0.0003) and showed a trend towards correlation with CRP levels (r = 0.447, P = 0.067). Resistin expression in muscle tissue was significantly higher in patients with inflammatory myopathies compared to controls, and resistin induced the expression of interleukins (IL)-1β and IL-6 and monocyte chemoattractant protein (MCP)-1 in mononuclear cells but not in myocytes. CONCLUSIONS: The results of this study indicate that higher levels of serum resistin are associated with inflammation, higher global disease activity index and muscle injury in patients with myositis-specific anti-Jo-1 antibody and patients with dermatomyositis. Furthermore, up-regulation of resistin in muscle tissue and resistin-induced synthesis of pro-inflammatory cytokines in mononuclear cells suggest a potential role for resistin in the pathogenesis of inflammatory myopathies.
- MeSH
- imunohistochemie MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé středního věku MeSH
- lidé MeSH
- myozitida krev imunologie patologie MeSH
- resistin krev MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
PURPOSE OF REVIEW: Arthritis is a well-recognized symptom of idiopathic inflammatory myopathies (IIM). We provide a summary of available data regarding the epidemiology, clinical characteristics, and autoantibody associations of joint involvement in various forms of IIM. RECENT FINDINGS: Arthritis is reported in 18-55% of patients with IIM. It is particularly frequent (20-70%) in those with antisynthetase syndrome (ASS); highest prevalence is associated with anti-Jo-1 positivity. Most common manifestation is non-erosive polyarthritis. X-ray erosions may be found occasionally in ASS, particularly in patients with overlap with rheumatoid arthritis (RA). Arthritis is often present at the time of IIM diagnosis and it may even precede the onset of muscle weakness. Arthritis may in some cases be the main disease manifestation responsible for the disease burden in patients with IIM. Arthritis is a frequent symptom of IIM. Polyarthritis of small joints of the hands is the most frequent clinical manifestation. Arthritis may be the first or dominant symptom in IIM and therefore patients may be initially misdiagnosed as having RA. Particularly in seronegative RA patients with interstitial lung disease or Raynaud's phenomenon, the possibility of IIM should be considered.
- MeSH
- artritida diagnóza epidemiologie MeSH
- lidé MeSH
- myozitida komplikace diagnóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
BACKGROUND: Interleukin-35 (IL-35) is a recently described heterodimeric cytokine that belongs to the IL-12 family and consists of p35 (IL-12a) and EBI3 (IL-27b) subunits. The expression of IL-35 in humans is inducible in response to inflammatory stimuli. Increased IL-35 levels were documented in several autoimmune inflammatory diseases, suggesting a possible immunomodulatory role in their pathogenesis. OBJECTIVES: The aim of this study was to explore a potential role of IL-35 in the pathogenesis of idiopathic inflammatory myopathies (IIM) by studying the expression of IL-35 subunits in muscle biopsy samples and by evaluating serum levels of IL-35 and their association with disease activity in IIM patients. METHODS: The expression of IL-35 subunits was studied in serial sections of 9 muscle biopsy samples [4 polymyositis (PM), 5 dermatomyositis (DM)] and in 7 non-inflammatory control muscle biopsies. Serum levels of IL-35 were measured in 23 PM, 28 DM and 15 cancer associated myositis (CAM) patients as well as in 40 healthy controls. Disease activity was evaluated using the Myositis Disease Activity Assessment Tool (MDAAT) and by serum muscle enzymes. RESULTS: Expression of both IL-35 subunits was evident in the inflammatory infiltrates in IIM muscle biopsies, while no IL-35 expression was observed in control muscle samples. IL-35 serum levels were increased in all IIM patients compared to healthy controls [median 119.5 (range 32.1-1074.5) vs 36.2 (range 1.5-86.5) pg/ml, P < 0.001]. There were no differences in IL-35 serum levels between myositis subgroups (DM, PM or CAM). Serum IL-35 levels correlated significantly with physician's assessment of global (r = 0.29, p = 0.021), muscle (r = 0.30, p = 0.017) and extramuscular (r = 0.30, p = 0.016) disease activity as well as creatine kinase (r = 0.26, p = 0.044) and lactate dehydrogenase (r = 0.40, p = 0.003) levels. There was a significant correlation with pulmonary activity in patients with interstitial lung disease (r = 0.39, p = 0.037). Serum IL-35 correlated negatively with duration of treatment (r = -34, p = 0.009). CONCLUSIONS: IL-35 is overexpressed in inflammatory infiltrates in muscle tissue and serum in IIM patients and there is correlation with several disease activity parameters. These data suggest potential role of locally produced IL-35 in the pathogenesis of inflammatory myopathies.
- MeSH
- biopsie MeSH
- dítě MeSH
- dospělí MeSH
- interleukiny krev metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- myozitida krev metabolismus patologie MeSH
- polymyozitida krev metabolismus patologie MeSH
- senioři MeSH
- svaly metabolismus patologie MeSH
- upregulace MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Idiopatické zánětlivé myopatie jsou heterogenní skupinou získaných zánětlivých onemocnění příčně pruhovaného svalstva, často doprovázené systémovými a orgánovými příznaky. Mezi nejčastější typy patří dermatomyozitida, polymyozitida, imunitně zprostředkovaná nekrotizující myopatie, s nádorem asociovaná myozitida, myozitida v rámci překryvných syndromů, juvenilní myozitida a myozitida s inkluzními tělísky. Základním klinickým projevem je většinou nebolestivá svalová slabost podmíněná zánětem a imunitními změnami v postiženém svalstvu. Z něho se do cirkulace uvolňují svalové enzymy a myoglobin. Mění se elektrické vlastnosti svalových vláken, které jsou pozorovatelné při elektromyografickém vyšetření. Převážná část nemocných má v séru přítomné autoprotilátky proti jaderným nebo cytoplazmatickým antigenům. Jejich přítomnost je většinou pro tato onemocnění velmi specifická a častá je asociace individuálních autoprotilátek s určitými klinickými projevy onemocnění. Pro některé pacienty, zejména s dermatomyozitidou, je zvýšená asociace s nádorovými chorobami, a u těchto nemocných je patrná významná souvislost s přítomností anti-TIF1γ a anti-NXP2 autoprotilátek. Diferenciální diagnostika zánětlivých myopatií bývá často složitá, záměna za jiné nezánětlivé onemocnění není výjimkou, a pečlivý diagnostický proces je nutností. Terapie směřuje k potlačení autoimunitní odpovědi pomocí glukokortikoidů a imunosupresiv. U větší části nemocných je odpověď na standardní léčbu nedostatečná a je nutné použít méně běžné či biologické léky nebo intravenózní imunoglobuliny. Nemocní s myozitidou s inkluzními tělísky neodpovídají na léčbu většinou vůbec nebo jen minimálně.
Idiopathic inflammatory myopathies form a heterogeneous group of acquired inflammatory diseases afflicting striated muscles. The disease is frequently accompanied by systemic and organ involvement. Dermatomyositis, polymyositis, cancer associated myositis, immune mediated necrotizing myopathy, myositis in overlap syndromes, juvenile myositis and inclusion body myositis are the most frequently encountered subtypes. The basic manifestation is usually painless muscle weakness brought about by inflammation and by other immune changes at the impacted muscles. Enzymes of muscle origin and myoglobin are found elevated in the circulation. There are changes in electrical properties of muscle fibers detected by EMG. A majority of patients have autoantibodies against nuclear or cytoplasmic antigens in their serum. They are often very specific for these diseases and frequently found in association with particular clinical presentations. For some patients with dermatomyositis the increased incidence of cancer is significantly associated with anti-TIF1γ and anti-NXP2 autoantibodies. Differential diagnostics of inflammatory myopathies is often difficult. Misdiagnosis for a non-inflammatory myopathy is not rare and therefore a very thorough diagnostic approach is necessary. Therapy aims to suppression of autoimmune response using glucocorticoids and immunosuppressive drugs. In large part of patients the response to standard treatment is not sufficient and less common synthetic compounds, biological drugs or intravenous immunoglobulins need to be used. Most patients with inclusion body myositis has limited or no effect of any treatment.
- MeSH
- autoprotilátky analýza MeSH
- diferenciální diagnóza MeSH
- glukokortikoidy aplikace a dávkování terapeutické užití MeSH
- imunosupresiva terapeutické užití MeSH
- lidé MeSH
- methotrexát aplikace a dávkování terapeutické užití MeSH
- myozitida * diagnóza patologie terapie MeSH
- nemoci svalů MeSH
- plíce patologie MeSH
- poruchy polykání MeSH
- prognóza MeSH
- zánět farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
