Clinical study| Volume 57, P13-19, November 2018

Statin-naïve anti-HMGCR antibody-mediated necrotizing myopathy in China

Published:September 08, 2018DOI:


      • Statin-naive anti-HMGCR cases.
      • Pattern of muscle MRI.
      • Early-onset cases are severer.


      This study aimed to clarify the phenotypes and therapeutic responses of statin-naïve anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibody-mediated necrotizing myopathy. Anti-HMGCR antibodies were tested with ELISA methodology in the sera sample of 98 patients meeting the idiopathic inflammatory myopathy criteria and with negative anti-signal recognition particle (SRP) antibody. Twenty-one statin-naïve patients with anti-HMGCR antibody were detected (21.4%), with onset age from 6 to 67 years old. Proximal weakness and neck flexion weakness was the core neurological feature. The average maximal creatine kinase (CK) level was 7968.6 ± 4408.7U/L. Muscle MR imaging showed edema (88.2%), moderate or severe fatty replacement (70.6%) and muscle atrophy (88.2%) in lower limbs. Fatty replacement was significantly more prominent in the medial and posterior musculature than the anterior musculature (p = 0.0013). Seven (33.3%) patients were treated with mono-glucocorticoid, and thirteen (61.9%) patients needed adjuvant immunosuppressant. Eight (38.1%) patients experienced symptom relapse. The early-onset patients (<50 years old) were found with higher CK levels, shorter duration course, poorer response to adjuvant immunosuppressant and more recurrent weakness than the late-onset patients (≥50 years old). As a conclusion, Statin-naïve anti-HMGCR antibody-mediated necrotizing myopathy may not be rare. Compared with late-onset statin-naïve patients with anti-HMGCR antibody-mediated necrotizing myopathy, early-onset patients presented severer clinical features and worse therapeutic responses.


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        • Hoogendijk J.E.
        • Amato A.A.
        • Lecky B.R.
        • et al.
        119th ENMC international workshop: trial design in adult idiopathic inflammatory myopathies, with the exception of inclusion body myositis, 10–12 October 2003, Naarden, The Netherlands.
        Neuromuscul Dis. 2004; 14: 337-345
        • Stenzel W.
        • Goebel H.H.
        • Aronica E.
        Review: immune-mediated necrotizing myopathies–a heterogeneous group of diseases with specific myopathological features.
        Neuropathol Appl Neurobiol. 2012; 38: 632-646
        • Allenbach Yves
        • Mammen Andrew L.
        • Benveniste Olivier
        • et al.
        224th ENMC International Workshop: Clinico-sero-pathological classification of immune-mediated necrotizing myopathies 14–16 October 2016, Zandvoort, The Netherlands.
        J Neuromuscul Dis. 2018; 28: 87-99
        • Ghirardello A.
        • Borella E.
        • Beggio M.
        • et al.
        Myositis autoantibodies and clinical phenotypes.
        Auto Immun Highlights. 2014; 5: 69-75
        • Betteridge Z.
        • McHugh N.
        Myositis-specific autoantibodies: an important tool to support diagnosis of myositis.
        J Intern Med. 2016; 280: 8-23
        • Christopher-Stine L.
        • Casciola-Rosen L.A.
        • Hong G.
        • et al.
        A novel autoantibody recognizing 200-kd and 100-kd proteins is associated with an immune-mediated necrotizing myopathy.
        Arthritis Rheum. 2010; 62: 2757-2766
        • Mammen A.L.
        • Chung T.
        • Christopher-Stine L.
        • et al.
        Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy.
        Arthritis Rheum. 2011; 63: 713-721
        • Tiniakou E.
        • Pinal-Fernandez I.
        • Lloyd T.E.
        • et al.
        More severe disease and slower recovery in younger patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy.
        Rheumatology (Oxford). 2017; 56: 787-794
        • Liang W.C.
        • Uruha A.
        • Suzuki S.
        • et al.
        Pediatric necrotizing myopathy associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies.
        Rheumatology. 2017; 56: 287-293
        • Watanabe Y.
        • Suzuki S.
        • Nishimura H.
        • et al.
        Statins and myotoxic effects associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies: an observational study in Japan.
        Medicine. 2015; 94e416
        • Musset L.
        • Miyara M.
        • Benveniste O.
        • et al.
        Analysis of autoantibodies to 3-hydroxy-3-methylglutaryl-coenzyme A reductase using different technologies.
        J Immunol Res. 2014; : 405956
        • Mammen A.L.
        • Casciola-rosen L.
        • Christopher-Stine L.
        • et al.
        Myositis-specific autoantibodies are specific for myositis compared to genetic muscle disease.
        Neurol Neuroimmunol Neuroinflamm. 2015; 2e172
        • Li W.
        • Zheng Y.
        • Zhang W.
        • et al.
        Progression and variation of fatty infiltration of the thigh muscles in Duchenne muscular dystrophy, a muscle magnetic resonance imaging study.
        Neuromuscul Disord. 2015; 25: 375-380
        • Kinali M.
        • Cirak V.A.-G.
        • Glover A.
        • et al.
        Muscle histology vs MRI in Duchenne muscular dystrophy.
        Neurology. 2011; 76: 346-353
        • Watanabe Y.
        • Uruha A.
        • Suzuki S.
        • et al.
        Clinical features and prognosis in anti-SRP and anti-HMGCR necrotizing myopathy.
        J Neurol Neurosurg Psychiatry. 2016; 87: 1038-1044
        • Mohassel P.
        • Mammen A.L.
        Statin-associated autoimmune myopathy and anti-HMGCR autoantibodies.
        Muscle Nerve. 2014; 48: 477-483
        • Allenbach Y.
        • Drouot L.
        • Rigolet A.
        • et al.
        Anti-HMGCR autoantibodies in European patients with autoimmune necrotizing myopathies: inconstant exposure to statin.
        Medicine. 2014; 93: 150-157
        • Alshehri A.
        • Choksi R.
        • Bucelli R.
        • et al.
        Myopathy with anti-HMGCR antibodies: Perimysium and myofiber pathology.
        Neurol Neuroimmunol Neuroinflamm. 2015; 2e124
        • Werner J.L.
        • Christopher-Stine L.
        • Ghazarian S.R.
        • et al.
        Antibody levels correlate with creatine kinase levels and strength in anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy.
        Arthritis Rheum. 2012; 64: 4087-4093
        • Ramanathan S.
        • Langguth D.
        • Hardy T.A.
        • et al.
        Clinical course and treatment of anti-HMGCR antibody-associated necrotizing autoimmune myopathy.
        Neurol Neuroimmunol Neuroinflamm. 2015; 2e96
        • Mammen A.L.
        Statin-associated autoimmune myopathy.
        N Engl J Med. 2016; 374: 664-669
        • Bergua C.
        • Chiavelli H.
        • Simon J.P.
        • et al.
        Immune-mediated necrotizing myopathy.
        Z Rheumatol. 2016; 75: 151-156
        • Ge Y.
        • Lu X.
        • Peng Q.
        • et al.
        Clinical characteristics of anti-3-hydroxy-3-methylglutaryl coenzyme A reductase antibodies in Chinese patients with idiopathic inflammatory myopathies.
        PLoS One. 2015; 10e0141616