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The patient was a 55-year-old man who was admitted to hospital with "progressive myalgia and weakness for 4 months, and exacerbated for 1 month". Four months ago, he presented with persistent shoulder girdle myalgia and elevated creatine kinase (CK) at routine physical examination, which fluctuated from 1 271 to 2 963 U/L after discontinuation of statin treatment. Progressive myalgia and weakness worsened seriously to breath-holding and profuse sweating 1 month ago. The patient was post-operative for renal cancer, had previous diabetes mellitus and coronary artery disease medical history, had a stent implanted by percutaneous coronary intervention and was on long-term medication with aspirin, atorvastatin and metoprolol. Neurological examination showed pressure pain in the scapularis and pelvic girdle muscles, and V- grade muscle strength in the proximal extremities. Strongly positive of anti-HMGCR antibody was detected. Muscle magnetic resonance imaging (MRI) T2-weighted image and short time inversion recovery sequences (STIR) showed high signals in the right vastus lateralis and semimembranosus muscles. There was a small amount of myofibrillar degeneration and necrosis, CD4 positive inflammatory cells around the vessels and among myofibrils, MHC-Ⅰ infiltration, and multifocal lamellar deposition of C5b9 in non-necrotic myofibrils of the right quadriceps muscle pathological manifestation. According to the clinical manifestation, imageological change, increased CK, blood specific anti-HMGCR antibody and biopsy pathological immune-mediated evidence, the diagnosis of anti-HMGCR immune-mediated necrotizing myopathy was unequivocal. Methylprednisolone was administrated as 48 mg daily orally, and was reduced to medication discontinuation gradually. The patient's complaint of myalgia and breathlessness completely disappeared after 2 weeks, the weakness relief with no residual clinical symptoms 2 months later. Follow-up to date, there was no myalgia or weakness with slightly increasing CK rechecked. The case was a classical anti-HMGCR-IMNM without swallowing difficulties, joint symptoms, rash, lung symptoms, gastrointestinal symptoms, heart failure and Raynaud's phenomenon. The other clinical characters of the disease included CK as mean levels >10 times of upper limit of normal, active myogenic damage in electromyography, predominant edema and steatosis of gluteus and external rotator groups in T2WI and/or STIR at advanced disease phase except axial muscles. The symptoms may occasionally improve with discontinuation of statins, but glucocorticoids are usually required, and other treatments include a variety of immunosuppressive therapies such as methotrexate, rituximab and intravenous gammaglobulin.
Subject(s)
Male , Humans , Middle Aged , Autoantibodies , Myositis/diagnosis , Autoimmune Diseases , Muscle, Skeletal/pathology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Necrosis/pathology , Muscular Diseases/drug therapyABSTRACT
Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) myopathy is one of the subtypes of immune-mediated necrotizing myopathy. Anti-HMGCR antibodies induce complement activation,subsequently resulting in myofiber necrosis,regeneration with autophagy abnormalities and mitochondrial changes. The age of onset is from children to adulthood. Some patients have a history of exposure to statins. Most patients are subacute onset. The patients with chronic progressive process, are more like muscular dystrophy. The main symptoms are proximal symmetrical weakness of limbs and usually accompanied with extra-muscle symptoms. The MRI showed muscle edema in all patients and fatty infiltrates in some patients. Myositis-specific auto-antibodies and muscle biopsies play key roles in diagnosis of HMGCR myopathy. Corticosteroids and immunosuppressants were first line therapy. Pediatric patients or patients with chronic course are usually refractory, and the efficacy of different combinations of immunosuppressants needs to be further investigated.
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ABSTRACT Idiopathic inflammatory myopathies (IIM) are a heterogenous group of treatable myopathies. Patients present mainly to the rheumatologist and neurologists, complaining of acute or subacute onset of proximal weakness. Extramuscular manifestations may occur, including involvement of the lungs, skin, and joints. Classically, the diagnosis used to be made based on the creatine kinase level increase, abnormalities in electroneuromyography and presence of inflammatory infiltrates in the muscle biopsy. Recently, the importance of autoantibodies has increased, and now they may be identified in more than half of IIM patients. The continuous clinicoseropathological improvement in IIM knowledge has changed the way we see these patients and how we classify them. In the past, only polymyositis, dermatomyositis and inclusion body myopathy were described. Currently, immune-mediated necrotizing myopathy, overlap myositis and antisynthetase syndrome have been considered the most common forms of IIM in clinical practice, increasing the spectrum of classification. Patients previously considered to have polymyositis, in fact have these other forms of seropositive IIM. In this article, we reviewed the new concepts of classification, a practical way to make the diagnosis and how to plan the treatment of patients suffering from IIM.
RESUMO As miopatias inflamatórias idiopáticas (MII) são um grupo heterogêneo de miopatias tratáveis. Os pacientes procuram principalmente o reumatologista e o neurologista, queixando-se de início agudo ou subagudo de fraqueza proximal. Manifestações extramusculares podem ocorrer, incluindo envolvimento dos pulmões, pele e articulações. Classicamente, o diagnóstico era feito com base na elevação dos níveis de creatina quinase, anormalidades na eletroneuromiografia e presença de infiltrados inflamatórios na biópsia muscular. Recentemente, a importância dos autoanticorpos aumentou, e agora eles podem ser identificados em mais da metade dos pacientes com MII. A contínua melhora clínico-soropatológica no conhecimento do MII mudou a forma como vemos esses pacientes e como os classificamos. No passado, apenas polimiosite, dermatomiosite e miopatia por corpos de inclusão eram descritas. Atualmente, a miopatia necrosante imunomediada, a miosite de sobreposição e a síndrome antissintetase têm sido consideradas as formas mais comuns de MII na prática clínica, aumentando o espectro de classificação. Pacientes previamente considerados como portadores de polimiosite, na verdade, têm uma dessas outras formas de MII soropositivas. Neste artigo, revisamos os novos conceitos de classificação, uma forma prática de fazer o diagnóstico e como planejar o tratamento de pacientes que sofrem de MII.
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Objective:To explore clinical characteristics and treatment of pediatric anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibody-positive myopathy.Methods:Two cases of pediatric anti-HMGCR antibody-positive myopathy admitted to the Department of Neurology, Shenzhen Children′s Hospital from January to July 2020 were retrospectively analyzed for their clinical manifestations, creatine kinase (CK), myositis autoantibody, electromyography (EMG), muscle pathology, muscle magnetic resonance imaging (MRI), and treatment information.Results:Both of them were female cases.Case 1 was 3 years and 11 months old and case 2 was 7 years and 9 months old.They used to be healthy without history of statin use.Case 1 showed chronic onset of the disease, and case 2 had a subacute onset.The main clinical manifestations were progressive symmetric proximal muscle weakness accompanied by myalgia.Case 1 developed skin rash but case 2 did not.Significantly increased CK level was detected in both of them, which increased by 27.3-48.0 and 66.7-77.4 times of the upper limit before treatment in case 1 and case 2, respectively.They were diagnosed as muscular dystrophy at the early stage.EMG results suggested myogenic injuries in 2 cases, and muscle MRI showed extensive muscle edema.The muscle pathology of the 2 cases suggested muscle necrosis with a small amount of inflammatory cell infiltration.After diagnosis, both of them were treated with Methylprednisolone combined with intravenous immunoglobulin.CK decreased significantly but remained high, and muscle weakness was improved but did not return to normal.Oral Prednisone was given after discharge and case 2 was additionally medicated with azathioprine.Conclusions:Compared with adult patients, the clinical characteristics of pediatric anti-HMGCR antibody-positive myopathy are mostly similar.However, children patients usually have no history of statins and are more difficult to treat, less effective and worse prognosis.In addition, children patients are more likely to be diagnosed with " muscular dystrophy" at the beginning of illness.Therefore, idiopathic myositis autoantibody should be examined to confirm the diagnosis for children suspected to be " muscular dystrophy" but not confirmed by genetic examination.
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Objective:To determine the clinical, pathological and imaging phenotypes of pediatric patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) myopathy to explore its diagnostic strategies.Methods:The clinical features of 10 pediatric patients with anti-HMGCR myopathy in the Department of Neurology, Peking University First Hospital from July 2014 to July 2021 were collected. Muscle biopsies were performed in all patients, with histological, enzymatic histochemical and immunohistochemical staining.Results:The male to female ratio was 6∶4, the age of onset was 3-16 (8.3±3.7) years, 2 cases had subacute onset, and 8 cases experienced chronic progressive onset. All patients presented with neck and proximal muscular weakness of all limbs. Skin rash was observed in 2 cases. Serum creatine kinase was 998-27 981 U/L. The electromyography results were available from 6 cases, who experienced myogenic changes. The muscle magnetic resonance imaging was performed in 5 cases and revealed muscle edema predominantly in posterior compartment of thigh, with mild fatty infiltrate in 2 cases. An initial diagnosis was limb-girdle muscular dystrophy in 7 cases, but with subsequently negative genetic testing. Muscle biopsies revealed scattered necrotic fibers and regenerating fibers, complement deposition in sarcolemma basement-membrane areas of non-necrotic fibers and a few of lymphocyte infiltrate in all specimens. Moreover, a high frequency of major histocompatibility complex Ⅰ expression in muscle fibers was observed in 9 cases, proliferation of connective tissue of endomysium in 8 cases, muscle fiber hypertrophy in 4 cases and vacuoles in 2 cases.Conclusions:Pediatric anti-HMGCR myopathy is frequently misdiagnosed as muscular dystrophy. Systematic consideration of anti-HMGCR myopathy and testing for myositis specific antibody in children with genetically unconfirmed muscular dystrophy may help the differential diagnosis.
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OBJECTIVE@#To investigate the classification of idiopathic inflammatory myopathies (IIM) based on clinical manifestations and myositis- specific antibodies using cluster analysis.@*METHODS@#We retrospectively analyzed the data of patients with IIM admitted in Nanfang Hospital in 2015-2019. The clinical data of the patients including serum creatine kinase (CK), interstitial lung disease (ILD), cancer, and myositis-specific antibodies were collected for two-step cluster analysis to identify the distinct clusters of patients, whose clinical characteristics were subsequently analysed.@*RESULTS@#A total of 71 patients with IIM were included in this study, including 30 (42.3%) with polymyositis (PM), 20 (28.2%) with classic dermatomyositis (DM), 16 (22.5%) with amyopathic dermatomyositis (CADM), and 5 (7.0%) with immune-mediated necrotizing myopathy (IMNM). Two-step cluster analysis identified 3 distinctive subgroups: Cluster 1 of 15 (51.7%) patients characterized by rash, positive anti-MDA5 antibody and hypoproteinemia ( < 0.05) with normal or slightly elevated CK level, mainly corresponding to CADM; Cluster 2 of 4 (57.1%) patients with significantly elevated CK and positive anti-SRP antibody ( < 0.001) corresponding to IMNM; and Cluster 3 of 17 (48.6%) patients consisting primarily of patients with PM, characterized by positivity for anti- aminoacyl transfer RNA synthetases antibodies (=0.022) corresponding to antisynthetase syndrome (ASS).@*CONCLUSIONS@#Patients with IIM can be divided into 3 subgroups based on their clinical and serological characteristics (especially myositis-specific antibodies), and among them ASS may represent an independent IIM subgroup with unique clinical characteristics.
Subject(s)
Humans , Antibodies , Autoantibodies , Dermatomyositis , Lung Diseases, Interstitial , Myositis , Retrospective StudiesABSTRACT
Idiopathic inflammatory myopathies (IIM) are a group of acquired immune myopathy,which mainly include polymyositis,dermatomyositis,amyopathic dermatomyositis,sporadic inclusion body myosistis (sIBM) and immune-mediated necrotizing myopathy,as well as some special types of antisynthetase syndrome,anti-signal recognition particle antibody positive necrotizing myopathy (NM),anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibody positive NM.The diagnosis of these different types of IIM mainly depends on clinical manifestations,antibody detection and muscle pathological techniques.Different types of IIM have different clinical manifestations,or overlapping manifestations.This article systematically describes the evolution of IIM types,the main antibodies to myositis,the pathological characteristics of muscles,the manifestations of various types and the treatment of myositis.In addition to sIBM,patients with most of the other types of IIM have good outcomes by early diagnosis,timely,correct and adequate drug treatment.
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Objective To explore clinical and muscular pathological features of statin-induced myopathy.Methods Nine patients were enrolled in this study,who were diagnosed as statin-induced myopathy by muscle biopsy in Peking University First Hospital from April,2012 to October,2014.The clinical data and pathological findings were analyzed.Results The exposure time to statins varied from 4 days to 4 years in the total of 9 patients,6 males and 3 females,with the average age of 63 ± 6 (55 to 74) years old.Three patients suffered from myalgia and 6 patients complained of weakness mainly at the proximal limbs,while no symptoms occured in 3 patients.Serum creatine kinase (CK) increased in all patients with the maximum value varied from 468 to 8 000 U/L.Serum myositis antibodies were tested in 7 patients and all were negative.Electromyogram was performed in six patients with myogenic damage found in 2 patients.MRI of bilateral thigh muscle was carried out in six patients with muscle edema and mild fatty infiltration found in 2 patients.All patients underwent skeletal muscle biopsy with histochemical and immunohistochemical staining.The main muscular pathological features were muscle fiber atrophy,necrosis,regeneration and increased lipid droplets.Ragged blue fiber,cytochrome C oxidase-negative muscle fibers and decreased NADH activity were observed in some patients.MHC-Ⅰ expressed in the sarcolemma of muscle fibers at various levels.Mild C5b-9 staining was found in the endomysium,capillary and cytoplasm.Symptoms and the level of CK were improved in 7 patients after discontinuing statins or changing to another statin,while the immunosuppressive therapy were used in 2 patients and shown to be effective.Conclusions Statin induced myopathy is self-limiting in most patients,with improvement after discontinuation of statins.Few patients with autoimmune necrotic myopathy need immunosuppressive therapy.
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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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We describe here a case of female patient who presented with mild proximal weakness, myalgia, and markedly elevated CPK, which could be ascribed to paraneoplastic necrotizing myopathy in association with ovarian adenocarcinoma. A histologic examination of the vastus lateralis muscle showed necrosis of muscle fibers without inflammatory cell infiltration. Her neurologic symptoms improved following tumor resection and systemic chemotherapy. Paraneoplastic necrotizing myopathy may be a presenting manifestation of malignancy, and early recognition and prompt treatment are crucial for the clinical improvement.