Cancer association as a risk factor for anti-HMGCR antibody-positive myopathy

Kadoya, Masato; Hida, Ayumi; Maeda, Mitsuaki; Taira, Kenichiro; Ikenaga, Chiseko; Uchio, Naohiro; Kubota, Akatsuki; Kaida, Kenichi; Miwa, Yusuke; Kurasawa, Kazuhiro; Shimada, Hiroyuki; Sonoo, Masahiro; Chiba, Atsuro; Shiio, Yasushi; Uesaka, Yoshikazu; Sakurai, Yasuhisa; Izumi, Toru; Inoue, Manami; Kwak, Shin; Tsuji, Shoji; Shimizu, Jun

doi:10.1212/nxi.0000000000000290

Cited by 83 publications

(79 citation statements)

References 21 publications

(41 reference statements)

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“…The risk doubles with anti-HMGCR antibodies, but in seronegative patients, it is more than eightfold higher than in the general population. Although studies in Japan seem to confirm the association between cancer and anti-HMGCR [45], it is not supported in all publications [31,46]. …”

Section: Defining Clinical Phenotypesmentioning

confidence: 97%

Statin-induced myalgia and myositis: an update on pathogenesis and clinical recommendations

Selva-O’Callaghan

Alvarado-Cárdenas

Pinal‐Fernandez

et al. 2018

Expert Review of Clinical Immunology

138

128

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Introduction Musculoskeletal manifestations are well-recognized side effects of treatment with statins. New advances in this field have appeared in recent years. This review focuses on the diagnosis of these conditions and their underlying pathogenesis, in particular immune-mediated necrotizing myopathy. Areas covered Clinical phenotypes including rhabdomyolysis, myalgia and/or mild hyperCKemia, self-limited toxin statin myopathy, and immune-mediated necrotizing myopathy are herein described. Therapeutic recommendations and a diagnostic algorithm in statin-associated myopathy are also proposed. The etiology and pathogenesis of statin-induced myopathy has mainly focused on the anti-HMGCR antibodies and the responsibility of the immune-mediated necrotizing myopathy is discussed. The fact that patients who have not been exposed to statins may develop statin-associated autoimmune myopathy with anti-HMGCR antibodies is also addressed. The literature search strategy included terms identified by searches of PubMed between 1969 and December 2017. The search terms ‘myositis’, ‘statin-induced autoimmune myopathy’, ‘immunemediate necrotizing myopathy’, ‘statins’, ‘muscular manifestations’, and ‘anti-HMGCR antibodies’ were used. Expert commentary Full characterization of the known phenotypes of statin toxicity and the specific role of the anti-HMGCR in those exposed and not exposed (i.e. juvenile forms) to statins and in some types of neoplasms is of paramount relevance.

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Section: Defining Clinical Phenotypesmentioning

confidence: 97%

Statin-induced myalgia and myositis: an update on pathogenesis and clinical recommendations

Selva-O’Callaghan

Alvarado-Cárdenas

Pinal‐Fernandez

et al. 2018

Expert Review of Clinical Immunology

138

128

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“…Specifically, autoantibody-negative IMNM has been associated with a markedly increased risk of malignancy (95%SCR CI: 8.35–24.41) [30••]. In contrast, anti-HMGCR myopathy may have a relatively weak association with cancer (95%SCR CI: from 0.4–2.4 to 1.02–6.07) [30••], although this has not been demonstrated in all cohorts [21••, 31•, 32•, 33••]. Finally, anti-SRP myopathy is not associated with cancer [13••, 16••, 30••, 33••, 34•].…”

Section: Cancer Associationmentioning

confidence: 99%

Immune-Mediated Necrotizing Myopathy

2018

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Purpose of Review Immune-mediated necrotizing myopathy (IMNM) is a type of autoimmune myopathy characterized by relatively severe proximal weakness, myofiber necrosis with minimal inflammatory cell infiltrate on muscle biopsy, and infrequent extra-muscular involvement. Here, we will review the characteristics of patients with IMNM. Recent Findings Anti-signal recognition particle (SRP) and anti-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) autoantibodies are closely associated with IMNM and define unique subtypes of patients. Importantly, the new European Neuromuscular Centre criteria recognize anti-SRP myopathy, anti-HMGCR myopathy, and autoantibody-negative IMNM as three distinct subtypes of IMNM. Anti-SRP myopathy patients have more severe muscle involvement, have more common extra-muscular features, and may respond best to immunosuppressive regimens that include rituximab. In contrast, anti-HMGCR myopathy is often associated with statin exposure and intravenous immunoglobulin treatment may be an effective treatment, even as monotherapy. Both anti-SRP and anti-HMGCR myopathy tend to be most severe in younger patients. Furthermore, children with these forms of IMNM may present with dystrophy-like features which are potentially reversible with immunosuppressant treatment. IMNM patients with either autoantibody may experience fatty replacement of muscle soon after disease onset, suggesting that intense and early immunosuppressant therapy may provide the best chance to avoid long-term disability. Summary IMNM is composed of anti-SRP myopathy, anti-HMGCR myopathy, and autoantibody-negative IMNM. Both anti-SRP and anti-HMGCR myopathy can cause severe weakness, especially in younger patients. Anti-SRP myopathy patients tend to have the most severe weakness and most prevalent extra-muscular features. Autoantibody-negative IMNM remains poorly described.

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“…Nonetheless, descriptive studies of anti-SRP IMNM do not report an increased incidence of malignancy. For patients with anti-HMGCR myopathy, one other study confirmed an increased risk of malignancy [18] and another one did not [28].…”

Section: Definition Of Immune Mediated Necrotizing Myopathymentioning

confidence: 98%

“…Finally, some series have found that there may be an increased risk of cancer in HMGCR-positive patients, and thus cancer screening is necessary [8,[18][19][20].…”

Section: Definition Of Immune Mediated Necrotizing Myopathymentioning

confidence: 99%