Acquired immune and inflammatory myopathies

Pestronk, Alan

doi:10.1097/bor.0b013e32834bab42

Cited by 130 publications

(118 citation statements)

References 52 publications

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“…In DM the inflammatory infiltrate comprises primarily CD4 + T cells, macrophages and small numbers of B cells and plasma cells, and is mainly perivascular and perimysial in distribution [22]. In addition, BDCA-2 + plasmacytoid dendritic cells, which secrete type 1 IFNs, are present in the perimysium and endomysium (Table 1) [40].…”

Section: Dermatomyositismentioning

confidence: 99%

Cytokines in immune-mediated inflammatory myopathies: cellular sources, multiple actions and therapeutic implications

Moran

Mastaglia

2014

Clinical and Experimental Immunology

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SummaryThe idiopathic inflammatory myopathies are a heterogeneous group of disorders characterised by diffuse muscle weakness and inflammation. A common immunopathogenic mechanism is the cytokine-driven infiltration of immune cells into the muscle tissue. Recent studies have further dissected the inflammatory cell types and associated cytokines involved in the immune-mediated myopathies and other chronic inflammatory and autoimmune disorders. In this review we outline the current knowledge of cytokine expression profiles and cellular sources in the major forms of inflammatory myopathy and detail the known mechanistic functions of these cytokines in the context of inflammatory myositis. Furthermore, we discuss how the application of this knowledge may lead to new therapeutic strategies for the treatment of the inflammatory myopathies, in particular for cases resistant to conventional forms of therapy.

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Section: Dermatomyositismentioning

confidence: 99%

Cytokines in immune-mediated inflammatory myopathies: cellular sources, multiple actions and therapeutic implications

Moran

Mastaglia

2014

Clinical and Experimental Immunology

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“…Muscle biopsy is most useful when the biopsy site is properly chosen (i.e., in a muscle that does not have clinical signs of advanced or end-stage disease but is also not minimally affected), the specimen is processed at an experienced laboratory, and the findings are interpreted in the context of the clinical picture. [1][2][3]24,25 In dermatomyositis, the inflammation is perivascular and is most prominently located in the interfascicular septae or the periphery of the fascicles. The muscle fibers undergo necrosis and phagocytosis -often in a portion of a muscle fasciculus or the periphery of the fascicleowing to microinfarcts that lead to hypoperfusion and perifascicular atrophy.…”

Section: Agnosismentioning

confidence: 99%

“…The residual perifascicular atrophy reflects the endofascicular hypoperfusion, which is most prominent at the periphery of the fascicles. 2,3,24,25 The activation of membrane attack complex, presumably by antibodies, triggers the release of proinflammatory cytokines, up-regulates adhesion molecules on endothelial cells, and facilitates migration of activated lymphocytes, including B cells, CD4+ T cells, and plasmacytoid dendritic cells, to the perimysial and endomysial spaces (Fig. 1E).…”

Section: Immunopathologymentioning

confidence: 99%

“…In dermatomyositis, complement C5b-9 membranolytic attack complex is activated early (before the destruction of muscle fibers is evident) and deposited on the endothelial cells, leading to necrosis, reduction of the density of endomysial capillaries, ischemia, and musclefiber destruction resembling microinfarcts [1][2][3][4][5][6]24,25,34 ; the remaining capillaries have dilated lumens to compensate for the ischemia 2,3,25 ( Fig. 1A through 1D).…”

Section: Immunopathologymentioning

confidence: 99%

“…The muscle fibers undergo necrosis and phagocytosis -often in a portion of a muscle fasciculus or the periphery of the fascicleowing to microinfarcts that lead to hypoperfusion and perifascicular atrophy. [1][2][3][4][5] Perifascicular atrophy, which is characterized by layers of atrophic fibers at the periphery of the fascicles, often with perivascular and interfascicular infiltrates, is diagnostic of dermatomyositis (or of overlap myositis, when the skin changes are absent or transient) [1][2][3][4][5]10,24,25 (Fig. 1A).…”

Section: Agnosismentioning

confidence: 99%

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Inflammatory Muscle Diseases

Young¹,

Finn²,

Reisin³

2015

N Engl J Med

140

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Clinical Features and Treatment Outcomes of Necrotizing Autoimmune Myopathy

et al. 2015

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IMPORTANCE Necrotizing autoimmune myopathy (NAM) is characterized pathologically by necrotic muscle fibers with absent or minimal inflammation. It is often accompanied by statin therapy, connective tissue diseases, cancer, and autoantibodies specific for signal recognition particle (SRP) or 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Data are limited concerning differences among etiologic subgroups and treatment outcomes in NAM. OBJECTIVES To describe the clinical, serologic, and electrophysiologic characteristics of NAM, compare patient subgroups, and determine clinical outcome predictors. DESIGN, SETTING, AND PARTICIPANTS We conducted a retrospective review of medical records for 63 adult Mayo Clinic patients assigned the clinical and histopathologic diagnosis of NAM from January 1, 2004, through December 31, 2013. Patients were stratified by presumed cause and autoantibody status. MAIN OUTCOMES AND MEASURES Clinical, electrophysiologic, and pathologic characteristics were collected and compared among patient subgroups. Predictors of response to treatment were identified by univariate logistic regression. RESULTS Lower extremity weakness predominated (46 [73%]). Distal weakness (26 [41%]), dysphagia (22 [35%]), and dyspnea (23 [37%]) were common. Twenty-two patients (35%) were receiving a statin medication at onset, 6 had cancer, and 3 had a connective tissue disease. The median creatine kinase level was 5326 U/L. In 13 patients (24%), SRP-IgG was detected, and in 17 patients (34%), HMGCR-IgG was detected (one-third of whom had not received statin medication). One patient was dual seropositive. Facial weakness was more common in SRP-IgG-positive patients. Myotonic discharges were more common in statin-associated NAM. Prednisone monotherapy was insufficient to control disease in most patients; 30 (90%) of 32 patients required 2 or more immunotherapeutic agents. Relapse occurred in 16 (55%) of 29 patients during immunosuppressant taper or discontinuation. Predictors of favorable outcome were male sex and use of 2 or more immunotherapeutic agents within 3 months of onset.CONCLUSIONS AND RELEVANCE Necrotizing autoimmune myopathy was idiopathic in half of this cohort with clinical and histopathologically defined disease. In the remainder, NAM was associated with statin medication, cancer, or connective tissue disease. One in 4 patients was SRP-IgG positive, and 1 in 3 was HMGCR-IgG positive. The disease was usually not controlled by corticosteroid monotherapy. Presentation, course, and outcomes did not differ significantly in seropositive, seronegative, and statin-associated cases. Early aggressive immunosuppressant therapy improved outcomes, and risk of relapse was high during medication dose reduction or withdrawal.

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Acquired immune and inflammatory myopathies

Abstract: Myopathology can be used to classify IIM. Identification of distinctive myopathologic changes in IIM can improve diagnostic and prognostic accuracy and focus treatment, therapeutic trials and studies of pathogenic factors.

Cited by 130 publications

References 52 publications

Cytokines in immune-mediated inflammatory myopathies: cellular sources, multiple actions and therapeutic implications

Cytokines in immune-mediated inflammatory myopathies: cellular sources, multiple actions and therapeutic implications

Inflammatory Muscle Diseases

Clinical Features and Treatment Outcomes of Necrotizing Autoimmune Myopathy

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