Rheumatology (Oxford). 2017 Feb;56(2):287-293. doi: 10.1093/rheumatology/kew386. Epub 2016 Nov 6.

Pediatric necrotizing myopathy associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies.


OBJECTIVE: Antibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) have recently been associated with immune-mediated necrotizing myopathy, especially in patients with statin exposure. As the data are very limited concerning phenotypes and treatment in paediatric patients, we aimed to identify the paediatric patients positive for anti-HMGCR antibodies and clarify their features and therapeutic strategies.
METHODS: We screened 62 paediatric patients who were clinically and/or pathologically suspected to have inflammatory myopathy for anti-HMGCR antibodies. We further re-assessed the clinical and histological findings and the treatment of the patients positive for anti-HMGCR antibodies.
RESULTS: We identified nine paediatric patients with anti-HMGCR antibodies (15%). This was more frequent than anti-signal recognition particle antibodies (four patients, 6%) in our cohort. The onset age ranged from infancy to 13 years. Five patients were initially diagnosed with muscular dystrophy, including congenital muscular dystrophy. Most patients responded to high-dose corticosteroid therapy first but often needed adjuvant immunosuppressants to become stably controlled.
CONCLUSION: Paediatric necrotizing myopathy associated with anti-HMGCR antibodies may not be very rare. Phenotypes are similar to those of adult patients, but a chronic slowly progressive course may be more frequent. Some patients share the clinicopathological features of muscular dystrophy indicating that recognizing inflammatory aetiology would be challenging without autoantibody information. On the other hand, most patients responded to treatment, especially those who were diagnosed early. Our results suggest the importance of early autoantibody testing in paediatric patients who have manifestations apparently compatible with muscular dystrophy in addition to those who have typical features of inflammatory myopathy.


抗3-ヒドロキシ-3-メチルグルタリルCoA還元酵素抗体(抗HMGCR抗体)は自己免疫介在性壊死性ミオパチー(IMNM)の病因自己抗体の一つである。当初、高脂血症治療薬であるスタチン製剤との関連が注目され、抗HMGCR抗体陽性IMNMの報告は成人症例にほぼ限られ、小児例の実態は明らかでなかった。本研究は小児抗HMGCR抗体陽性IMNMの臨床・病理学的特徴を明らかにすることを目的に行われた。2010 - 2015年に筋炎統合的診断研究プロジェクトに登録された炎症性筋疾患疑いの小児患者62例において抗HMGCR抗体を解析し、同抗体は9例(15%)で検出された。これら9例のうち5例は慢性的な臨床経過をたどり、筋ジストロフィーと暫定診断されていた。筋病理学的にも半数の症例で筋ジストロフィー様の中等度ないし高度の筋内鞘線維化と脂肪浸潤を伴う壊死・再生像が観察された。治療に関しては、副腎皮質ステロイド薬や免疫抑制剤、免疫グロブリンなどが使用され、特に発症早期に治療を開始した症例でより良好な反応が見られる傾向があった。 本研究で抗HMGCR抗体陽性IMNMの小児例は少なからず存在することが示された。また臨床病理学的に筋ジストロフィーと類似する点がある一方、IMNMには免疫修飾療法の有効性が見込まれるため、筋炎が鑑別診断として第一に考えられる患者だけでなく、小児期発症の病因未確定の筋ジストロフィー疑い患者においても、抗HMGCR抗体を含む自己抗体測定を積極的に行うことが望ましいと考えられた。

PMID:  27818386