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



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.



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.



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.
Department of Pediatrics, Kaohsiung Medical University Hospital.|Department of Pediatrics, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Wen-Chen
WC
Liang
Department of Genome Medicine Development, Medical Genome Center.|Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry.
Akinori
A
Uruha
Department of Neurology, Keio University School of Medicine, Tokyo.
Shigeaki
S
Suzuki
Department of Pediatrics, Koshigaya Hospital, Dokkyo Medical University, Saitama.
Nobuyuki
N
Murakami
Department of Pediatrics, Koshigaya Hospital, Dokkyo Medical University, Saitama.|Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
Eri
E
Takeshita
Department of Pathology, Kaohsiung Medical University Hospital.
Wan-Zi
WZ
Chen
Department of Pediatrics.|Department of Laboratory Medicine.|Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung.|Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.
Yuh-Jyh
YJ
Jong
Department of Genome Medicine Development, Medical Genome Center.|Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry.|Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
Yukari
Y
Endo
Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
Hirofumi
H
Komaki
Department of Pediatrics, Shiga Medical Center for Children, Shiga.
Tatsuya
T
Fujii
Department of Infectious disease, Immunology and Allergy, Saitama Children's Medical Center, Saitama.
Yutaka
Y
Kawano
Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
Madoka
M
Mori-Yoshimura
Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
Yasushi
Y
Oya
Department of Neurology, Huashan Hospital, Fudan University.
Jianying
J
Xi
Department of Genome Medicine Development, Medical Genome Center.|Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry.|Department of Neurology, Huashan Hospital, Fudan University.
Wenhua
W
Zhu
Department of Neurology, Huashan Hospital, Fudan University.|Department of Neurology, Jing'an District Center Hospital of Shanghai, Shanghai, China.
Chongbo
C
Zhao
Department of Neurology, Keio University School of Medicine, Tokyo.
Yurika
Y
Watanabe
Department of Neurology, Keio University School of Medicine, Tokyo.|Cosmic Corporation, Research and Development Section, Tokyo.
Keisuke
K
Ikemoto
Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry.|Department of Education, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi.
Atsuko
A
Nishikawa
Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry.|Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Kohei
K
Hamanaka
Department of Genome Medicine Development, Medical Genome Center.|Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry.
Satomi
S
Mitsuhashi
Department of Neurology, Keio University School of Medicine, Tokyo.
Norihiro
N
Suzuki
Department of Genome Medicine Development, Medical Genome Center nishino@ncnp.go.jp.|Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry.
Ichizo
I
Nishino
D000293:Adolescent; D001323:Autoantibodies / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000276:immunology*; D007223:Infant; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009220:Myositis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D001323:Autoantibodies; C553220:HMGCR protein, human; D006903:Hydroxymethylglutaryl CoA Reductases
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR); immune-mediated necrotizing myopathy; major histocompatibility complex (MHC); membrane attack complex (MAC); muscular dystrophy; paediatrics