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Dermatomyositis, polymyositis, inclusion body myositis and myositis overlap syndromes are systemic immune disorders of unknown origin with muscle weakness and elevated values of creatinkinase in the serum. Muscle biopsy is pivotal for a proper clinical diagnosis. Extramuscular findings at the skin, the joints or internal organs (lung, heart) are characteristic for the different clinical presentations of dermato- or polymyositis and are usually absent in inclusion body myositis. With the exception of inclusion body myositis myositis-associated autoantibodies are frequently present and associated with distinct clinical manifestations (e. g. antisynthetase syndrome). The rate of malignancy is elevated for several years after onset of myositis. Especially in polymyositis an appropriate differential diagnosis of infectious, endocrine, metabolic or neuromuscular causes of muscle disease is necessary. Glucocorticosteroids are the first choice of treatment in dermato- or polymyositis. Methotraxate, azathioprine, cyclophosphamamide, i.v. immunoglobulins and other drugs are used in diseases courses with continuous high dose requirement of corticosteroids.
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PMID:[Inflammatory muscle diseases: dermatomyositis, polymyositis, and inclusion body myositis]. 1620 Apr 4

This guideline presents recommendations for the diagnosis and treatment of dermatomyositis, polymyositis and sporadic inclusion body myositis (sIBM) according to the best available evidence. Characteristic skin abnormalities can be sufficient for the diagnosis of dermatomyositis. In case of doubt, a skin biopsy is advisable. A muscle biopsy is indicated when other examinations are inconclusive and the musculature is involved. The working group considers screening for cancer to be required in adults with dermatomyositis and presents recommendations for the way that this should be done. At least one-third of all patients with polymyositis has, or will develop, an associated inflammatory connective tissue disease. If a patient with a connective tissue disease develops symmetrical, proximal muscle weakness in the course of weeks or months, this may be assumed to be due to polymyositis. In the absence ofpre-existing connective tissue disease, demonstration of a mononuclear cell infiltrate in muscle tissue is a prerequisite for the diagnosis ofpolymyositis. The histopathology of muscle tissue is used as the gold standard for the diagnosis of sIBM. The practice guideline presents criteria for the concept 'activity' of myositis. Disease activity serves as a guideline for the treatment of polymyositis and dermatomyositis. The treatment of choice for dermatomyositis and polymyositis is high-dose prednisone. Physical activity does not have a negative effect on the course of these diseases. The long-term prognosis ofdermatomyositis and polymyositis is not well known. The clinical course of sIBM is slowly progressive.
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PMID:[The practice guideline 'Dermatomyositis, polymyositis and sporadic inclusion body myositis']. 1620

The idiopathic inflammatory myopathies (IIM) are systemic connective tissue diseases in which autoimmune pathology is suspected to promote chronic muscle inflammation and weakness. We have performed low to high resolution genotyping to characterize the allelic profiles of HLA-A, -B, -Cw, -DRB1, and -DQA1 loci in a large population of North American Caucasian patients with IIM representing the major clinicopathologic groups (n = 571). We confirmed that alleles of the 8.1 ancestral haplotype were important risk markers for the development of IIM, and a random forests classification analysis suggested that within this haplotype, HLA-B*0801, DRB1*0301 and/ or closely linked genes are the principal HLA risk factors. In addition, we identified several novel HLA factors associated distinctly with 1 or more clinicopathologic groups of IIM. The DQA1*0201 allele and associated peptide-binding motif (KLPLFHRL) were exclusive protective factors for the CD8+ T cell-mediated IIM forms of polymyositis (PM) and inclusion body myositis (IBM) (pc < 0.005). In contrast, HLA-A*68 alleles were significant risk factors for dermatomyositis (DM) (pc = 0.0021), a distinct clinical group thought to involve a humorally mediated immunopathology. While the DQA1*0301 allele was detected as a possible risk factor for IIM, PM, and DM patients (p < 0.05), DQA1*03 alleles were protective factors for IBM (pc = 0.0002). Myositis associated with malignancies was the most distinctive group of IIM wherein HLA Class I alleles were the only identifiable susceptibility factors and a shared HLA-Cw peptide-binding motif (AGSHTLQWM) conferred significant risk (pc = 0.019). Together, these data suggest that HLA susceptibility markers distinguish different myositis phenotypes with divergent pathogenetic mechanisms. These variations in associated HLA polymorphisms may reflect responses to unique environmental triggers resulting in the tissue pathospecificity and distinct clinicopathologic syndromes of the IIM.
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PMID:Immunogenetic risk and protective factors for the idiopathic inflammatory myopathies: distinct HLA-A, -B, -Cw, -DRB1 and -DQA1 allelic profiles and motifs define clinicopathologic groups in caucasians. 1626 9

Dermatomyositis is an inflammatory myopathy characterized by muscle weakness and inflammation. In contrast to polymyositis and inclusion body myositis, humoral immune mechanisms appear to contribute to the pathogenesis of dermatomyositis. A 56-year-old man with dermatomyositis resistant to conventional therapies was treated with 6 weekly infusions of the anti-CD-20 monoclonal antibody, rituximab, at a dosage of 100 mg/m in addition to other agents. The patient demonstrated a remarkable clinical response as indicated by an increase in muscle strength and a decline in creatine kinase enzymes. B-cell depletion therapy with rituximab used alone or in combination with other immunosuppressive therapies may be a viable option in patients with dermatomyositis as well as other autoimmune diseases refractory to current therapies.
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PMID:Rituximab in the treatment of refractory dermatomyositis. 1635 73

Inclusion body myositis (IBM), a condition characterised by progressive muscle weakness and inclusion bodies visible on muscle biopsy, is the most common type of myopathy in patients over 50 years of age. However, it is not only under diagnosed but frequently misdiagnosed as polymyositis and hence wrongly treated with steroids. In the evaluation of progressive weakness in older Caucasian males, IBM should be an important diagnostic consideration. Treatment-resistant 'polymyositis' in patients over 50 years of age is often IBM. If there is no histological confirmation, the diagnostic criteria allow for a category of 'possible IBM'. Sometimes, the diagnosis is missed because of the slow progression of the disease and a lack of suspicion on the part of physicians. The following case report and literature review will explore many of these issues.
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PMID:Inclusion body myositis: an underdiagnosed myopathy of older people. 1636 43

The objective was to report a clinical, pathological and muscle magnetic resonance (MR) study of an Italian family with an autosomal dominant inclusion body myopathy (AD-IBM). Eight subjects (age range 20-56 years; 5 females and 3 males) belonging to four generations were studied. Onset of disturbances (distal weakness at lower limbs) ranged from 20 to 28 years. CK levels were increased to five times. Only in an early stage oedema of involved muscles has been demonstrated by muscle MR. Quadriceps femoris was characteristically spared; in the last phases a mild involvement of the vasti became evident with persistent sparing of the rectus femori. Rimmed vacuoles and hyperphosphorylated tau filaments were evident at muscle biopsy. Linkage analysis excluded the association of the disease to chromosome loci 14q11, 17p13.1, 2p13, 19p13. The study suggests that quadriceps sparing is a characteristic feature also of AD-IBM. This finding could represent a muscle-image hallmark helpful in diagnosis of autosomal dominant muscular disorders.
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PMID:Clinical and muscle magnetic resonance imaging study of an Italian family with autosomal dominant inclusion body myopathy not linked to known genetic loci. 1638 63

The diagnostic aspects of sporadic inclusion-body myositis (s-IBM), and a few comments on our own approach to its treatment, are presented to foster the goals of this symposium, which was organized to provoke new ideas concerning the cause and treatment of this currently unsolvable disease. s-IBM is the most common, progressive, debilitating muscle disease beginning in persons over age 50 years, and it is more common in men. Diagnostic parameters reviewed are clinical, muscle-biopsy histochemistry, electrophysiologic and CSF evaluations. Overall, the degenerative phenomena in s-IBM muscle fibers seem to be the major cause of the progressive, unstoppable weakness, rather than the lymphocytic inflammation. Available treatments are of only slight, temporary benefit for only some s-IBM patients, indicating a desperate need for definitive therapies.
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PMID:Inclusion-body myositis: clinical, diagnostic, and pathologic aspects. 1643 41

Mitochondrial changes are frequently encountered in sporadic inclusion-body myositis (s-IBM). Cytochrome c oxidase (COX)-deficient muscle fibers and large-scale mitochondrial DNA (mtDNA) deletions are more frequent in s-IBM than in age-matched controls. COX deficient muscle fibers are due to clonal expansion of mtDNA deletions and point mutations in segments of muscle fibers. Such segments range from 75 microm to more than 1,000 microm in length. Clonal expansion of the 4977 bp "common deletion" is a frequent cause of COX deficient muscle fiber segments, but many other deletions also occur. The deletion breakpoints cluster in a few regions that are similar to what is found in human mtDNA deletions in general. Analysis in s-IBM patients of three nuclear genes associated with multiple mtDNA deletions, POLG1, ANT1 and C10orf2, failed to demonstrate any mutations. In s-IBM patients with high number of COX-deficient fibers, the impaired mitochondrial function probably contribute to muscle weakness and wasting. Treatment that has positive effects in mitochondrial myopathies may be tried also in s-IBM.
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PMID:Mitochondrial abnormalities in inclusion-body myositis. 1643 45

Immunogenic inflammatory myopathies are a heterogeneous group of acquired muscle disorders. Clinical and morphological characteristics are on one side muscle weakness, on the other side inflammatory infiltrates in muscle biopsy. Three main groups of different pathogenesis and course can be subdivided: The treatment of inflammatory myopathies is predominantly based on empiric data. Baseline drugs are Corticosteroids and Immunosuppressives. High dose intravenous Immunoglobulins (IVIG) are an important additional therapeutic possibility, especially in inclusion body myositis.
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PMID:[Immunogenic myositis]. 1646 3

The idiopathic inflammatory myopathies embody the largest group of acquired and potentially treatable causes of skeletal muscle weakness. The three major groups of this disorder are polymyositis (PM), dermatomyositis (DM), and inclusion body myositis. Corticosteroids continue to be the mainstay of initial treatment in the majority of cases of PM/DM. The treatment of refractory disease can be challenging despite the utilization of the medications currently available. We report two patients with refractory DM who were treated with infliximab. We describe their presentation, clinical course, treatment, and outcomes.
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PMID:Treatment of early and refractory dermatomyositis with infliximab: a report of two cases. 1673 25


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