SEARCH · PubMed Health

Results for “Inflammatory myopathy”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed2002

Inflammatory myopathies.

Inflammatory myopathies are the result of infiltration of inflammatory cells into striated muscle, with or without an association with an underlying cause. Two broad classifications are IIMs and secondary inflammatory myopathies associated with other diseases. Standard diagnostic criteria for inflammatory myopathy include the presence of weakness or loss of specific muscle group function, an increase in CK, EMG changes associated with muscle membrane instability, and histologic evidence of inflammation. Not all these criteria, however, must be present. Fresh-frozen biopsy from two proximal muscles is recommended for biopsy confirmation. IIM can either focally affect head or neck muscles or be more diffuse. MMM is an immune-mediated disease characterized by a humoral antibody produced against the unique type IIM and type I variant mvofibers of masticatory muscles of dogs, which causes inflammation and loss of function of the muscles of mastication. Idiopathic polymyositis can affect focal muscle groups (extraocular, laryngeal) or present as multifocal or diffuse involvement of skeletal muscle in the cat and dog. Familial canine DM is an inflammatory disease of the striated muscle, skin, and vasculature in young Collies, Shetland Sheepdogs (Shelties), and, rarely, Collie-crossbred dogs. Immunosuppressive therapy is the key to successful treatment. Protozoal parasitic myopathies are the most common cause of clinically relevant secondary inflammatory myopathies. The degree of systemic involvement is often the limiting factor to successful treatment. Early recognition of the clinical signs for proper diagnostic testing and institution of appropriate therapy can result in a rewarding outcome in treating inflammatory myopathies in the cat and dog.

Animals↗

PubMed1992

Inflammatory myopathies.

Inflammatory myopathies encompass a wide range of disorders. This article deals with the idiopathic inflammatory myopathies. Classification and diagnostic criteria proposed by Bohan and Peter are still widely used. Diagnosis is based on clinical features, muscle enzyme abnormalities, electromyographic findings and muscle biopsy results. There are known associations with malignancy and lung disease which may affect the prognosis. Management consists of the prudent use of corticosteroids. In refractory cases, cytotoxic agents, cyclosporin and plasmapheresis have been used.

Adrenal Cortex Hormones↗

PubMed2005

Muscle regeneration, inflammation, and connective tissue expansion in canine inflammatory myopathy.

Inflammatory myopathies (IMs) are relatively common in dogs, and canine IMs have many similarities to human IMs. The aim of this work was to analyze aspects of the pathogenesis of canine IM with an ultimate goal of establishing canine IM as a model for human IM. Muscle biopsies from 16 dogs with a histological diagnosis of IM were analyzed to determine degree of muscle regeneration, presence of eosinophils, expression of selected cytokines and chemokines, and extent of fibrosis. Regeneration, as shown by staining for developmental myosin heavy chain, was more extensive than evidenced with hematoxylin-eosin staining in most cases of canine IM. Expression of mRNA encoding transforming growth factor-beta (TGF-beta) and eotaxin 3 was upregulated in all cases evaluated. Eosinophils were abundant in most cases, and the connective tissue was variably expanded, as demonstrated by the distribution of the ubiquitous extracellular matrix proteins collagen VI and fibrillin. The extensive regeneration demonstrates that muscle may survive this adverse environment if inflammation and fibrosis can be stopped or reduced.

Animals↗

PubMed2000

MRI in inflammatory myopathies.

Inflammatory myopathies encompass a group of acquired muscle disorders caused by infectious agents (bacteria, viruses, fungi and parasitic agents) or autoimmune processes (polymyositis, dermatomyositis and other types). In suspected infection sonography, CT and MRI are all able to show edema and fluid collections in soft tissues and muscles; sonography and CT may help guidance of a needle aspiration to establish a correct diagnosis. By offering better tissue differentiation, MRI appears to be more efficient than sonography and CT in diagnosing and managing autoimmune myopathies. MRI is indeed very sensitive to the presence of water and edema, and appears to be a very good indicator for an early diagnosis of diseases. MRI may also help to evaluate the extent and number of lesions, to guide a biopsy in an area of active disease and finally to follow the evolution under therapy.

Autoimmune Diseases↗

PubMed2006

Sarcolemma-specific autoantibodies in canine inflammatory myopathy.

Inflammatory myopathies (IM) are relatively common in dogs with an increased incidence in the Boxer and Newfoundland breeds. Here, we show that a high proportion of affected Boxers and Newfoundlands have circulating autoantibodies against unknown sarcolemma antigens, that are muscle-specific but not species specific. We further show that the autoantigen can be extracted from muscle membranes with non-ionic detergent, and that such detergent extracts can be used in a sensitive ELISA for detection and quantitation of antibodies. The relatively high incidence of IM with autoantibodies in selected breeds of dogs indicates a genetic predisposition for a particular form of IM. In these breeds, this form of IM could be diagnosed and monitored with a simple serum assay.

Animals↗

PubMed2007

The cell-specific expression of metalloproteinase-disintegrins (ADAMs) in inflammatory myopathies.

Inflammatory cell invasion and cytokine activation are important steps in the pathogenesis of immune-mediated diseases of muscle. Metalloproteinase-disintegrins (ADAMs) are considered to play a critical role in leukocyte migration by promoting cellular adhesion, cleavage of molecules of the extracellular matrix and shedding of membrane bound cytokines. Here, we report the expression patterns of ADAM8, ADAM9, ADAM10, ADAM12, ADAM17 and ADAM19 in cultured human myoblasts and peripheral blood mononuclear cells (PBMCs) in vitro, as well as in biopsies from patients suffering from polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM) and non-inflammatory controls. We observed an in vitro downregulation of the RNAs of ADAM10, ADAM17 and ADAM19 in myoblasts after stimulation with various pro- and anti-inflammatory mediators, whereas in PBMCs an RNA upregulation of ADAM9, ADAM10, ADAM17 and ADAM19 was detectable under identical conditions. In human muscle biopsies, invading CD3+ T lymphocytes expressed ADAM17 and ADAM19, whereas macrophages co-localized to ADAM8, as detected by immunohistochemistry. Transfection of PBMCs with ADAM19 single interfering RNA and incubation with a metalloproteinase inhibitor suggest proteolytic activity of ADAM19 and involvement in the shedding of tumor necrosis factor-alpha. No differences in the cellular expression profiles between PM, DM and IBM were found, whereas the sections from non-inflammatory controls did not reveal any positive immunoreactivity for ADAMs, except for ADAM10, which is localized exclusively to muscle fibres. Our results suggest that certain ADAMs are expressed by specific cell populations during the genesis of immune-mediated diseases of human muscle.

ADAM Proteins↗

PubMed2003

CBA/J mice infected with Trypanosoma cruzi: an experimental model for inflammatory myopathies.

Idiopathic inflammatory myopathies are inflammatory disorders of unknown origin, characterized by muscle weakness. The aim of our study was to establish and characterize an animal model for chronic inflammatory myopathy which would permit investigations of the role of T-cells in chronic myositis as well as of the mechanisms for muscle weakness in chronic inflammatory muscle disorders. CBA/J mice were infected with the protozoan parasite Trypanosoma cruzi. Immunohistochemistry was used to characterize the distribution and composition of inflammatory infiltrates, and demonstrated a chronic focal inflammation comprised mainly of T-cells and macrophages in infected mice. The inflammatory infiltrates were predominantly found in the endomysium and, to a lesser extent, in perivascular areas. CD8(+) T-cells were found to have invaded nonnecrotic muscle fibers. Degenerating muscle fibers were also found, as well as an increased number of central muscle nuclei. The murine model described in this article may be useful in studying certain aspects of idiopathic inflammatory myopathies such as the role of T-cells in chronic muscle inflammation and chronic myocytotoxicity.

Animals↗

PubMed2003

Cytokines, chemokines, and cell adhesion molecules in inflammatory myopathies.

The inflammatory myopathies include dermatomyositis (DM), polymyositis (PM), and sporadic inclusion-body myositis (s-IBM). In DM, the main immune effector response appears to be humoral and directed against the microvasculature, whereas in both PM and s-IBM, cytotoxic CD8+ T cells and macrophages invade and eventually destroy nonnecrotic muscle fibers expressing major histocompatibility complex class I. The need for more specific and safer therapies in inflammatory myopathies has prompted researchers to better decipher the molecular events associated with inflammation and muscle fiber loss in these diseases. The complex specific migration of leukocyte subsets to target tissues requires a coordinated series of events, namely activation of leukocytes, adhesion to the vascular endothelium, and migration. Cell adhesion molecules (CAM) and chemokines play a major role in this multistep process. In addition, cytokines by stimulating CAM expression and orchestrating T-cell differentiation also influence the immune response. This review focuses on recent advances in defining the molecular events involved in leukocyte trafficking in inflammatory myopathies. Specific topics include a concise summary of clinical features, pathological findings and immunopathology observed in inflammatory myopathies, background information about cytokines, chemokines and cell adhesion molecules, and the expression of these molecules in inflammatory myopathies.

Cell Adhesion Molecules↗

PubMed2006

Update on idiopathic inflammatory myopathies.

The inflammatory myopathies are a group of acquired diseases, characterized by an inflammatory infiltrate of the skeletal muscle. On the basis of clinical, immuno-pathological and demographic features, three major diseases can be identified: dermatomyositis (DM); polymyositis (PM); and inclusion body myositis (IBM). New diagnostic criteria have recently been introduced, which are crucial for discriminating between the three different subsets of inflammatory myopathies and for excluding other disorders. DM is a complement-mediated microangiopathy affecting skin and muscle. PM and IBM are T cell-mediated disorders, where CD8-positive cytotoxic T cells invade muscle fibres expressing MHC class I antigens, thus leading to fibre necrosis. In IBM, vacuolar formation with amyloid deposits are also present. This article summarizes the main clinical, laboratory, electrophysiological, immunological and histologic features as well as the therapeutic options of the inflammatory myopathies.

Autoantibodies↗

PubMed1992

Clinical, immunopathologic, and therapeutic considerations of inflammatory myopathies.

The inflammatory myopathies encompass a group of heterogenous muscle diseases which have in common an acquired myopathy with histological signs of endomysial inflammation. We present evidence based on recently emerged clinical, histologic, immunopathologic, demographic and therapeutic observations that these myopathies comprise three major and distinct groups: polymyositis (PM), dermatomyositis (DM), and inclusion-body myositis (IBM). Immune-mediated mechanisms characteristic for each group appear to play a primary role in the pathogenesis of these diseases. In DM there is an intramuscular microangiopathy mediated by the C5b-9 membranolytic attack complex, leading sequentially to loss of capillaries, muscle ischemia, muscle fiber necrosis and perifascicular atrophy. In contrast, in PM and IBM the muscle fiber injury is initiated by sensitized CD8+ cytotoxic T cells that recognize MHC-I restricted muscle antigens, leading to phagocytosis and fiber necrosis. Among the viruses implicated in the cause of inflammatory myopathies, only the retroviruses, HIV, HTLV-1 and simian retroviruses, have been convincingly associated with PM. Retroviruses, therefore, appear to be the leading group of viruses capable of triggering these diseases. The treatment of inflammatory myopathies has been largely empirical. A detailed therapeutic plan based on our experience with a large number of patients is presented. Patients with bona fide PM or DM respond to steroids to some degree and for some period of time. In contrast, patients with IBM do not respond to any therapy and the disease should be suspected when a patient with presumed PM has failed treatment. Methotrexate and cyclophosphamide are disappointing. Cyclosporine and Azathioprine are commonly used but they are of uncertain benefit. Plasmapheresis is ineffective. High-dose intravenous immunoglobulin is a promising new therapeutic modality.

Adult↗

PubMed2007

A local antigen-driven humoral response is present in the inflammatory myopathies.

The inflammatory myopathies are putative autoimmune disorders characterized by muscle weakness and the presence of intramuscular inflammatory infiltrates. Although inclusion body myositis and polymyositis have been characterized as cytotoxic CD8(+) T cell-mediated diseases, we recently demonstrated high frequencies of CD138(+) plasma cells in the inflamed muscle tissue of patients with these diseases. To gain a deeper understanding of the role these B cell family members play in the disease pathology, we examined the molecular characteristics of the H chain portion of the Ag receptor. Biopsies of muscle tissue were sectioned and tissue regions and individual cells were isolated through laser capture microdissection. Ig H chain gene transcripts isolated from the sections, regions, and cells were used to determine the variable region gene sequences. Analysis of these sequences revealed clear evidence of affinity maturation in that significant somatic mutation, isotype switching, receptor revision, codon insertion/deletion, and oligoclonal expansion had occurred within the B and plasma cell populations. Moreover, analysis of tissue regions isolated by laser capture microdissection revealed both clonal expansion and variation, suggesting that local B cell maturation occurs within muscle. In contrast, sequences from control muscle tissues and peripheral blood revealed none of these characteristics found in inflammatory myopathy muscle tissue. Collectively, these data demonstrate that Ag drives a B cell Ag-specific response in muscle in patients with dermatomyositis, inclusion body myositis, and polymyositis. These findings highlight the need for a revision of the current paradigm of exclusively T cell-mediated intramuscular Ag-specific autoimmunity in inclusion body myositis and polymyositis.

Adult↗

PubMed1988

Inflammatory myopathies.

The inflammatory myopathies are a heterogeneous group of disorders with recent evidence demonstrating differences in clinical features, pathologic changes, pathogenesis, and response to therapy. The inflammatory myopathies generally produce predominantly proximal, symmetric muscle weakness and wasting. Additional criteria for diagnosis include elevated serum muscle enzymes, myopathic features on EMG, and muscle biopsy abnormalities, including muscle fiber necrosis, degeneration, and inflammatory infiltrates. Inclusion body myositis is distinctive in that distal weakness is most commonly equal to or greater than proximal weakness and muscle biopsy reveals rimmed, cytoplasmic vacuoles, eosinophilic inclusions in the cytoplasm, and nucleus and abnormal filamentous structures. Autoimmune mechanisms seem likely to be involved in the pathogenesis of these disorders and viral infection may be etiologically involved in some of these diseases. The differences in the site of immune-mediated damages suggest an angiography in dermatomyositis while direct muscle fiber involvement is more likely in polymyositis and inclusion body myositis. Therapy of these disorders is similar although some, particularly inclusion body myositis, may be particularly resistant to therapy. Prednisone is currently recommended as the first treatment with azathioprine or methotrexate added after 3 months if steroids are ineffective.

Dermatomyositis↗

PubMed2002

Muscle biopsy findings in inflammatory myopathies.

The inflammatory myopathies encompass a heterogeneous group of acquired muscle diseases characterized clinically, by muscle weakness, and histologically, by inflammatory infiltrates within the skeletal muscles. The group of these myopathies comprise three major and discrete subsets: polymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM). Each subset retains its characteristic clinical, immunopathologic, and morphologic features regardless of whether it occurs separately or in connection with other systemic diseases. Although the diagnosis of these disorders is based on the combination of clinical examination, electromyographic data, serum muscle enzyme levels, various autoantibodies, and the muscle biopsy findings, the muscle biopsy offers the most definitive diagnostic information in the majority of the cases. This article summarizes the main histologic features that characterize PM, DM, or IBM and emphasizes the main pitfalls associated with interpretation of the biopsies.

Biopsy↗

PubMed2003

Increase in transglutaminase 2 in idiopathic inflammatory myopathies.

Idiopathic inflammatory myopathies (IMs), including dermatomyositis (DM), polymyositis (PM), and sporadic inclusion body myositis (s-IBM), are characterized by inflammatory cell infiltration in muscle tissue and muscle fiber destruction, which leads to muscle weakness. Although the cause of IMs is unclear, an autoimmune pathogenesis may be involved in initiating the muscle inflammation. Recently, we have found an aberrant expression of transglutaminase 2 (TGase 2) in s-IBM, which is closely associated with insoluble inclusion body formation. TGase 2 is a cross-linking enzyme that generates a conformational change of molecules via a covalent isopeptide bond. The increase in the level of TGase 2 expression and the inappropriate presentation of substrates/cross-linked aggregates to the immune system may contribute to the autoimmune aspects of IMs. We investigated whether or not an increase in TGase 2 expression is a common factor in muscle inflammation. Duchenne muscular dystrophy (DMD) and normal tissues were employed as controls. Using immunocytochemistry and quantitative RT-PCR, the level of TGase 2 expression was found to be specifically increased in PM and DM, but not in DMD and normal controls. Therefore, the targeting of TGase inhibition in IMs will be a challenging therapeutic approach that should be investigated in the near future.

Case-Control Studies↗

PubMed2004

[Use of muscular MRI in inflammatory myopathies].

PURPOSE: Inflammatory myopathies include polymyositis (PM), dermatomyositis (DM) and inclusion body myositis (IBM) which differ in terms of clinical, immuno-histological presentations, evolution and treatment. Diagnosis is based on the muscular biopsy but histological distinction between PM and IBM can be difficult; biopsies can be insufficient as well as during follow-up to detect active areas within the muscle. CURRENT KNOWLEDGE AND KEY POINTS: Muscular MRI is an important tool both in the diagnosis and the follow-up of IMM in the following circumstances: Distinction between PM and IBM: fatty infiltration and involvement of the anterior group of the thighs are characteristic of IBM whereas isolated inflammation and involvement of the three thighs or posterior muscle groups are characteristic of PM. Biopsy guidance on the inflammatory lesions depicted on the STIR sequence either initially or after a non-conclusive biopsy. To differentiate, active disease from steroid myopathy. FUTURE PROSPECTS AND PROJECTS: Several multicentric trials are in development both in spectro and morphologic MRI to study hypoxic phenomenon in early course of IMM and muscular volume evaluation both in normal subjects, congenital or acquired myopathies.

Diagnosis, Differential↗

PubMed2002

Molecular profiles of inflammatory myopathies.

OBJECTIVE: To describe the use of large-scale gene expression profiles to distinguish broad categories of myopathy and subtypes of inflammatory myopathies (IM) and to provide insight into the pathogenesis of inclusion body myositis (IBM), polymyositis, and dermatomyositis. METHODS: Using Affymetrix GeneChip microarrays, the authors measured the simultaneous expression of approximately 10,000 genes in muscle specimens from 45 patients in four major disease categories (dystrophy, congenital myopathy, inflammatory myopathy, and normal). The authors separately analyzed gene expression in 14 patients limited to the three major subtypes of IM. Bioinformatics techniques were used to classify specimens with similar expression profiles based on global patterns of gene expression and to identify genes with significant differential gene expression compared with normal. RESULTS: Ten of 11 patients with IM, all normals and nemaline myopathies, and 10 of 12 patients with Duchenne muscular dystrophy were correctly classified by this approach. The various subtypes of inflammatory myopathies have distinct gene expression signatures. Specific sets of immune-related genes allow for molecular classification of patients with IBM, polymyositis, and dermatomyositis. Analysis of differential gene expression identifies as relevant to disease pathogenesis previously reported cytokines, major histocompatibility complex class I and II molecules, granzymes, and adhesion molecules, as well as newly identified members of these categories. Increased expression of actin cytoskeleton genes is also identified. CONCLUSIONS: The molecular profiles of muscle tissue in patients with inflammatory myopathies are distinct and represent molecular signatures from which diagnostic insight may follow. Large numbers of differentially expressed genes are rapidly identified.

Adolescent↗

PubMed2000

Increased expression of beta-chemokines in muscle of patients with inflammatory myopathies.

Idiopathic inflammatory myopathies (IIM) are muscle diseases of autoimmune pathogenesis characterized by mononuclear cell infiltration within muscle tissue. Since immune cell homing and accumulation at the site of antigenic challenge is usually mediated by chemokines, we evaluated the expression of 2 beta-chemokines--monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha)--by immunohistochemistry and polymerase chain reaction in muscles of polymyositis, inclusion body myositis, and dermatomyositis patients, and related their expression to immunopathological alterations in muscle. MCP-1 and MIP-1alpha transcripts were detected by PCR in all IIM muscles, but not in controls. By immunohistochemistry, the chemokines were found in all IIM muscle sections located in infiltrating inflammatory cells and also in neighboring extracellular matrix. The extent to which extracellular matrix was filled by each chemokine differed in each disease. In view of the known ability of chemokines to bind extracellular matrix and their possible synthesis by extracellular matrix components, we suggest that chemokine storage in the extracellular matrix can act as a microenvironmental factor amplifying lymphocyte activation and migration, thereby maintaining the autoimmune attack against unknown muscle antigens.

Chemokine CCL2↗

PubMed2006

Potential therapeutic targets for idiopathic inflammatory myopathies.

The inflammatory myopathies essentially comprise three diseases with different immunopathologic features. Dermatomyositis (DM) is a complement-mediated microangiopathy. The immune response in polymyositis (PM) and sporadic inclusion body myositis (IBM) is a CD8+ T-cell-mediated cellular reaction against an unknown muscle fiber antigen. The multiple immune factors that guide inflammatory cell diapedesis and trafficking have been elucidated over the past two decades. Many of these molecules can now be targeted by monoclonal antibodies and other pharmacologic approaches. Randomized controlled trials are being started on a number of new agents to find out whether more specific immune interventions than the currently used glucocorticosteroids can treat DM and PM patients with fewer side effects, and may represent a first treatment modality for IBM, an entity unresponsive to all currently available pharmacological treatments.

Adrenal Cortex Hormones↗