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Objective:To summarize the clinical, thigh magnetic resonance (tMRI) and electromyographic (EMG) characteristics in patients with immune-mediated necrotizing myopathy (IMNM).Methods:A total of 32 IMNM patients who were admitted to the Department of Neurology from April 2019 to April 2021 were enrolled at the First Medical Centre of Chinese PLA General Hospital. According to the type of antibody, the patients were divided into anti-SRP antibody positive (SRP +) group, anti-HMGCR antibody positive (HMGCR +) group and seronegative (SN) group. The gender, age, course of disease, myositis antibodies, extramuscular manifestations, EMG were collected and analyzed among three groups. The characteristics of skeletal muscle were assessed by tMRI inflammatory edema and fat infiltration scores. Analysis of variance, Kruskal-Wallis test and Chi-square test were used to compare the differences in different clinical characteristics and tMRI scores among the three groups. When there was a statistical difference among the three groups, the comparison between the two groups was corrected by the Bonferroni method. Result:(1) Of the 32 patients, 20 were females (62.5%).The median age of onset was 47±14 years, 25 (78.1%) patients had an acute or subacute course.There were 17 (53.1%) with SRP +, 8 (25.0%) with HMGCR +, and 7 (21.9%) with MSAs (myositis specific antibodies) negative. Anti-Ro52 antibody was the most common combined antibody (12/32, 37.5%), among which 10 were in SRP +group.(2) The CK of all patients were elevated, median was 5 948 (4 229, 7 664) U/L. There was no statistical difference of MMT scores among three groups. The proximal limb score was lower than distal limb ( P<0.01). The axial muscle score was lower than the distal limb score ( P<0.05).(3) Extramuscular manifestations of HMGCR + group were lower than those of the other two groups (12.5% vs. 71.4% and 76.5%, P<0.017). Rash (60.0% vs.14.3%, P<0.05) and interstitial pulmonary diseases (70.0% vs. 14.3%, P<0.05) were more common in patients with anti-SRP coexistence with anti-Ro52 than those with isolated anti-SRP. Connective tissue disease was more common in SN group (57.1% vs. 11.8% and 0, P<0.017).(4) tMRI showed fascial edema of SN group was more obvious than that of the other two groups ( P<0.017). There was no statistical difference in the degree of fat infiltration and inflammatory edema among three groups, but SRP + group had more cases of early fat infiltration.(5) Myotonic potentials (25.0% vs. 0 and 0, P<0.017) and compound repetitive discharges (CRDs) (50.0% vs. 5.9% and 0, P<0.017) were common in HMGCR + group. Proteomic analysis found significantly different expressed proteins in skeletal muscle of patients with myotonic potentials or CRDs were associated with cytoskeleton, cell junction and extracellular matrix. Conclusion:IMNM with pure anti-SRP antibody positive and anti-HMGCR positive were mainly affected by skeletal muscles. Those who were co-positive for anti-SRP antibody and anti-Ro52 antibody had more extramuscular manifestations, which might be a special subtype of SRP + group. This study proposed for the first time that myofascial inflammatory edema is an early sign of SN-IMNM injury. EMG of HMGCR +group were more prone to myotonia potential and CRDs.
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Objective@#To investigate the clinical features of anti-signal recognition particle (SRP) antibody-positive patients with dermatomyositis/clinically amyopathic dermatomyositis (DM/CADM) .@*Methods@#Clinical data were collected from 90 patients with DM/CADM, who were hospitalized at the Department of Dermatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from June 2015 to July 2017. Immunoblotting assay was performed to determine the serum level of anti-SRP antibody in these patients. Statistical analysis was carried out using t test and Chi-square test.@*Results@#Of the 90 patients with DM/CADM, 11 (12.2%) were positive for serum anti-SRP antibody, including 6 with DM and 5 with CADM. Among 82 adult patients with DM/CADM, the prevalence of malignant tumors was significantly higher in the patients with anti-SRP antibody than in those without (7/9 vs. 31.5%[23/73], χ2 = 7.394, P = 0.006) . The 11 patients with anti-SRP antibody had typical DM skin lesions, and their cutaneous dermatomyositis disease area and severity index (CDASI) was 18.1 ± 2.9. The prevalence of "angel wings sign" (aliform erythema on the trunk) was significantly higher in the patients with anti-SRP antibody than in those without (7/11 vs. 29.9%[20/67], Fisher′s exact test, P = 0.028) . The positive rate of antinuclear antibody was significantly higher in the patients with anti-SRP antibody than in those without (4/8 vs. 16.7%[13/78], χ2 = 6.053, P = 0.014) . Magnetic resonance imaging of muscles of both thighs of the 10 patients with anti-SRP antibody (6 with DM and 4 with CADM) showed the presence of abnormal signals in the thigh muscle group in 8, swelling of the muscle group in 2, subcutaneous edema in 2, myofascial swelling in 1, and no abnormities in 2. No interstitial lung disease or myocardial involvement was observed in the patients with anti-SRP antibody.@*Conclusions@#The anti-SRP antibody-positive patients with DM/CADM showed a high prevalence of "angel wings sign" , and a high risk of malignant tumors. Early detection of the anti-SRP antibody in patients with DM/CADM is helpful to predict the occurrence of malignant tumors.
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Miopatía Necrotizante Autoinmune (MNA) fue reconocida como nuevo sub-grupo de miositis luego de observar en biopsias musculares la presencia de necro-sis con escaso o ausente infiltrado inflamatorio, sumado a la expresión de dos an-ticuerpos específicos de miositis (Anticuerpo anti Partícula de Reconocimiento de Señal, anti-SRP; y Anticuerpo anti Hidroxi-3-metilglutaril-CoA reductasa, anti-HM-GCR), ambos fuertemente asociados al hallazgo histológico descrito y a fenotipos clínicos característicos a cada anticuerpo, los cuales comparten importantes simi-litudes representadas por severa debilidad muscular proximal, gran elevación de creatinkinasa (CK), escasa manifestación de síntomas y signos extramusculares, y resistencia al uso de inmunosupresión habitual. Si bien en primera instancia los criterios de clasificación propuestos estaban basados en la histología, la obser-vación de necrosis en otros subgrupos de miositis, sumado a la homogeneidad del comportamiento clínico de pacientes que expresaban anticuerpos anti-SRP o anti-HMGCR independiente de la histología presentada, llevó en el año 2016 al Grupo de Trabajo del Centro Europeo Neuromuscular (ENMC) a establecer crite-rios diagnósticos de MNA basados en el comportamiento clínico (debilidad mus-cular proximal con CK total elevada) más la presencia del anticuerpo respectivo (anti-SRP o anti-HMGCR), reservando la necesidad de realizar biopsia muscular en el caso que la serología resulte negativa, siendo así reconocidas tres entidades distintas de MNA: Miopatía anti-SRP, Miopatía anti-HMGCR y Miopatía Necroti-zante seronegativa. La presente revisión expresa el actual conocimiento de MNA y sus subtipos, refiriéndose a aspectos históricos, clínicos, histológicos, inmuno-patológicos, y de pronóstico y tratamiento.
Necrotizing autoinmune myopathy (NAM) was recognized as a new sub-group of myositis after the observation of necrosis with mild or absent inflam-matory infiltrates in muscle biopsies, in addition of expression of two specific myositis antibodies (antiSRP and antiHMGCR), which are strongly associated to the mentioned hystologic findings, with different clinical phenotypes depending on the presence of each antibody, but sharing some features like severe proximal muscle weakness, significant elevation of creatin phosphokinase (CK), mild ex-tramuscular involvement and resistance to commonly used immunosupressants. The first proposed approach to classification criteria was hystology-based, none-theless the observation of necrosis in some other types of myositis and the homo-geneity of clinical features in patients expressing antiSRP or antiHMGCR despite the hystologic findings led to a new classification scheme leaded by the European Neuromuscular Center in 2016, which recognizes thre different clinical entities of NAM, based on the antibody expression plus the presence of proximal muscle weakness, relying hystology to a secondary place thus eliminating the need for immediate biopsy to stablish a diagnosis: those are antiSRP myopathy, antiHMG-CR myopathy and seronegative necrotizing myopathy, being the last one the only needing muscle biopsy. The present review shows the actual knowledge about NAM and its subtypes, referring to hystoric, clinical, hystologic, immunopatholog-ic, prognostic and therapeutic issues.
Subject(s)
Humans , Autoimmune Diseases/pathology , Myositis/pathology , Autoimmune Diseases/immunology , Muscular Diseases , Myositis/diagnosis , Myositis/physiopathology , Myositis/therapy , Myositis/epidemiology , Necrosis/immunology , Necrosis/pathologyABSTRACT
Objective To characterize the clinical,electrophysiology and neuropathological features of 4 cases with immune-mediated necrotizing myopathy (IMNM).Methods We retrospectively analyzed the clinical,electrophysiology,neuropathological characteristics of 4 IMNM patients with muscular and skin biopsy in our department during 4 years (from January 2011 to January 2014).Results Among these 4 patients,2 were men and 2 were women (aged 37 to 58 years) with disease duration ranging from 1 month to 60 months.Two patients were with acute onset and 2 with chronic onset.All 4 patients had proximal muscle weakness with three patients with cervical flexor muscle weakness and one with respiratory muscles weakness and noninvasive ventilator assisted respiration.One patient had interstitial lung disease.The anti-signal recognition particle antibodies were strong positive in all 4 patients.Muscle biopsy showed group necrotizing and regenerating fibers in one patient and few scattered necrotizing and regenerating fibers in the other 3 patients.Both muscle fiber hypertrophy and muscle fiber atrophy together with proliferation of connective tissue on endomysium could be viewed in all 4 patients.However,very few inflammatory cells were detectable in patients.One patient was treated with corticosteroids and the other three were treated with combination of corticosteroids and immunosuppressant drugs.Conclusions IMNM is characterized by heterogeneity at disease onset,severity and ilnvolvement of muscles with,however,similary pathological changes including the presence of numerous necrotic and regenerating fibers with little or none inflammation.Corticosteroid and/or immunosuppressant is effective for patients.
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ObjectiveWe report the clinical and pathological features of 8 Chinese myopathy patients with antibodies to the signal recognition particle(SRP).MethodsSerum myositis antibody profiles were tested with immunoblotting.Muscle biopsies were performed for histological,enzyme histochemical and immunohistochemical stainings.The first antibody in the immunohistochemical staining was mouse anti-human monoclonal antibodies including CD8,CD20,CD68,MHC- Ⅰ and CD31.ResultsEight cases showed stark positive of anti SRP antibody,3 of them with positive anti Ro-52 antibody.The muscle biopsies showed necrotic and regenerative muscle fibers associated with infiltration of macrophage,but scattered T lymphocytes in 2 patients.Two of them presented with fiber hypertrophy and proliferation of connective tissue.There were some fibers with positive MHC-Ⅰexpression.Capillaries were almost normal.Conclusion The muscle weakness of myopathy with antibodies to SRP presents as a chronic progressive course and could associate with lung involvement.Fiber necrosis and regeneration are the main myopathological features,which can mimic muscular dystrophy in some cases.
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Myopathies associated with anti-signal-recognition particle (SRP) antibodies usually present with severe muscle weakness and exhibit necrotizing myopathy with little inflammation pathologically. Here we report a case of a 61-year-old man who presented with subacute progressive proximal muscle weakness, dysarthria, and dysphagia. Although polymyositis was expected clinically, muscle biopsy revealed myopathic changes with degenerating fibers without definite inflammation. Further laboratory study revealed that the patient was positive for anti-SRP antibodies.