Inflammatory Muscle Diseases

Dalakas, Marinos C.

doi:10.1056/nejmra1402225

Cited by 633 publications

(668 citation statements)

References 78 publications

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“…The clinical presentation is heterogenous and at times difficult to distinguish from other inflammatory myopathies (muscle weakness and atrophy), motor‐neuron disease (asymmetry), and muscular dystrophies (slowly progressive disease) 3. In two large observational studies, the mean age of onset has been reported to be 59 ± 9 and 61 years, respectively 9, 11.…”

Section: Clinical Presentationmentioning

confidence: 99%

“…IBM affects males more frequently (3:1), shows an overall prevalence of approximately 4‐15/1000000 (35‐71/1000000 > age 50, respectively), is noticably frequent in Western Australia, Japan, Norway, Olmsted County (Minnesota, USA), and is especially rare in Turkey and India 3, 24, 25, 26, 27, 28, 29, 30, 31. In Japan, the number of diagnosed IBM cases has steadily increased since 1991, whereas the number of PM cases has remained constant 32.…”

Section: Epidemiologymentioning

confidence: 99%

“…Histopathological hallmarks of IBM muscle feature both myodegenerative multi‐protein aggregates as well as endomysial lymphocytic infiltrates 2, 3, 4. Several lines of evidence suggest that inflammatory mechanisms precede myodegeneration,8 but so far a precise answer and sound evidence is lacking as discussed below in detail.…”

Section: Pathomechanisms In Ibmmentioning

confidence: 99%

“…Inclusion body myositis (IBM) is a progressive slow‐onset inflammatory myopathy that is characterized by the concomitant presence of multi‐focal myofiber‐surrounding lymphocytic infiltrates as well as vacuolar myodegeneration 1, 2, 3, 4. Together with dermatomyositis (DM), polymyositis (PM), necrotizing autoimmune myositis (NAM) and overlap myositis (OM), IBM belongs to the heterogenous group of inflammatory myopathies and, amongst individuals 50 years of age and older, it is considered as a relatively frequent disorder 3, 5.…”

Section: Introductionmentioning

confidence: 99%

“…Together with dermatomyositis (DM), polymyositis (PM), necrotizing autoimmune myositis (NAM) and overlap myositis (OM), IBM belongs to the heterogenous group of inflammatory myopathies and, amongst individuals 50 years of age and older, it is considered as a relatively frequent disorder 3, 5. The underlying interrelationship between the inflammatory component of the disease and the observed multi‐protein aggregation remains elusive and subject to vigorous debate 3, 6, 7, 8. Unlike other inflammatory myopathies, IBM presents mainly refractory toward immunosuppressive therapy and at present, there is no effective treatment available 5, 9, 10.…”

Section: Introductionmentioning

confidence: 99%

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Immune and myodegenerative pathomechanisms in inclusion body myositis

Keller

Schmidt

Lünemann

2017

Ann Clin Transl Neurol

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Inclusion Body Myositis (IBM) is a relatively common acquired inflammatory myopathy in patients above 50 years of age. Pathological hallmarks of IBM are intramyofiber protein inclusions and endomysial inflammation, indicating that both myodegenerative and inflammatory mechanisms contribute to its pathogenesis. Impaired protein degradation by the autophagic machinery, which regulates innate and adaptive immune responses, in skeletal muscle fibers has recently been identified as a potential key pathomechanism in IBM. Immunotherapies, which are successfully used for treating other inflammatory myopathies lack efficacy in IBM and so far no effective treatment is available. Thus, a better understanding of the mechanistic pathways underlying progressive muscle weakness and atrophy in IBM is crucial in identifying novel promising targets for therapeutic intervention. Here, we discuss recent insights into the pathomechanistic network of mutually dependent inflammatory and degenerative events during IBM.

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Section: Clinical Presentationmentioning

confidence: 99%

Section: Epidemiologymentioning

confidence: 99%

Section: Pathomechanisms In Ibmmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Immune and myodegenerative pathomechanisms in inclusion body myositis

Keller

Schmidt

Lünemann

2017

Ann Clin Transl Neurol

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Association of Statin Exposure With Histologically Confirmed Idiopathic Inflammatory Myositis in an Australian Population

et al. 2018

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IMPORTANCE Statin medications are widely prescribed for cardiovascular risk reduction. Myalgia and rhabdomyolysis are well-recognized adverse effects of statins, and they resolve with the cessation of statin therapy. Idiopathic inflammatory myositis (IIM) is a heterogeneous group of autoimmune myopathies that may also be associated with statin use. Recently, statin-associated autoimmune myopathy has been recognized as a distinct entity with the presence of specific autoantibodies against hydroxymethylglutaryl-coenzyme A reductase, which results in a necrotizing myositis that does not resolve with cessation of statin therapy and requires treatment with immunosuppressive agents. OBJECTIVE To examine the association between histologically confirmed IIM and current exposure to statin medications. DESIGN, SETTING, AND PARTICIPANTS Population-based case-control study using the South Australian Myositis Database of all histologically confirmed cases of IIM diagnosed between 1990 and 2014 in patients 40 years or older (n = 221) and population-based controls from the North West Adelaide Health Study (n = 662), matched by age and sex in a 3:1 ratio of controls to cases. Data analysis using conditional logistic regression was performed from June 1, 2016, to July 14, 2017. EXPOSURES Current statin medication use. MAIN OUTCOMES AND MEASURES Unadjusted and adjusted (for diabetes and cardiovascular disease) odds ratios and 95% CIs for likelihood of inflammatory myositis. RESULTS A total of 221 IIM cases met the inclusion criteria with a mean (SD) age of 62.2 (10.8) years, and 132 (59.7%) were female. Statin exposure at the time of IIM diagnosis was 68 of 221 patients (30.8%) and 142 of 662 matched controls (21.5%) (P = .005). There was an almost 2-fold increased likelihood of statin exposure in patients with IIM compared with controls (adjusted odds ratio, 1.79; 95% CI, 1.23-2.60; P = .001). Similar results were observed when patients with necrotizing myositis were excluded from the analysis (adjusted odds ratio, 1.92; 95% CI, 1.29-2.86; P = .001). CONCLUSIONS AND RELEVANCE In this large population-based study, statin exposure was significantly associated with histologically confirmed IIM. Given the increased use of statins worldwide and the severity of IIM, increased awareness and recognition of this potentially rare adverse effect of statin exposure is needed.

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Skeletal Muscle Involvement in Antisynthetase Syndrome

et al. 2017

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IMPORTANCE Antisynthetase syndrome, characterized by myositis, interstitial lung disease, skin rash, arthropathy, and Raynaud phenomenon, is a clinical entity based on the presence of aminoacyl transfer RNA synthetase (ARS) antibodies in patients' serum. However, antisynthetase syndrome is not included in the histological subsets of idiopathic inflammatory myopathies.OBJECTIVE To elucidate the clinical features of myositis in patients with antisynthetase syndrome. DESIGN, SETTING, AND PARTICIPANTSIn this cohort study, muscle biopsy and blood samples were collected from 460 patients with idiopathic inflammatory myositis from various regional referral centers throughout Japan between October 2010 and December 2014. Data were analyzed in March 2016.EXPOSURES Six different anti-ARS antibodies were detected in serum by RNA immunoprecipitation. Line blot assay and protein immunoprecipitation were also performed. HLA-DRB1 alleles were genotyped. MAIN OUTCOMES AND MEASURESThe main outcomes were muscle manifestations and histological findings. Predisposing factors, extramuscular symptoms, and follow-up information were also studied. RESULTSOf 460 patients with idiopathic inflammatory myopathies, 51 (11.1%) had anti-ARS antibodies. Of this subset, 31 (61%) were women, with a mean (SD) age at disease onset of 60.2 (16.1) years. Among 6 different anti-ARS antibodies, only 1-the anti-OJ antibody-was not detected by line blot assay but by RNA immunoprecipitation. There were no significant HLA-DRB1 alleles associated with anti-ARS antibodies. All 51 patients presented with muscle limb weakness; 14 (27%) had severe limb weakness, 17 (33%) had neck muscle weakness, 15 (29%) had dysphagia, and 15 (29%) had muscle atrophy. Although patients with anti-OJ antibodies showed severe muscle weakness, the clinical presentations of antisynthetase syndrome were relatively homogeneous. In histology, perifascicular necrosis, the characteristic finding of antisynthetase syndrome, was found in 24 patients (47%). Myositis with anti-ARS antibodies responded to the combination of immunosuppressive therapy with favorable outcomes. Interstitial lung disease, found in 41 patients (80%), was more closely associated with mortality than myositis. CONCLUSIONS AND RELEVANCEAlthough clinical presentations of antisynthetase syndrome were relatively homogeneous, anti-OJ antibodies were associated with severe muscle involvement. Antisynthetase syndrome is a clinical and histological subset among idiopathic inflammatory myopathies.

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Inflammatory Muscle Diseases

Cited by 633 publications

References 78 publications

Immune and myodegenerative pathomechanisms in inclusion body myositis

Immune and myodegenerative pathomechanisms in inclusion body myositis

Association of Statin Exposure With Histologically Confirmed Idiopathic Inflammatory Myositis in an Australian Population

Skeletal Muscle Involvement in Antisynthetase Syndrome

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