Clinicopathological and Imaging Differences Between Pediatric and Adult Patients with Anti-hydroxy-3-methyl-glutaryl-coenzyme A Reductase Necrotizing Myopathy

Overview

Journal Clin Rheumatol

Publisher Springer

Specialty Rheumatology

Date 2024 Nov 19

PMID 39562394

Authors

Mengting Yang

Yikang Wang

Yawen Zhao

JingChu Yuan

Yiming Zheng

Hongjun Hao

Wei Zhang

Zhaoxia Wang

Yun Yuan

Affiliations

Soon will be listed here.

Abstract

We aimed to elucidate the clinicopathological and imaging differences between pediatric and adult patients with anti-hydroxy-3-methyl-glutaryl-coenzyme A reductase (anti-HMGCR) myopathy. A series of 111 patients with anti-HMGCR myopathy were divided into pediatric (33 patients, onset age < 18 years) and adult (78 patients, onset age ≥ 18 years) groups. Clinical, imaging, and pathological characteristics were compared between the groups. Overall median age at onset was 40 years. Median duration of disease was 12 months. The male:female ratio was 41:70. Prevalence of statin exposure was 0% in the pediatric group and 21% in the adult group (P < 0.001). The prevalence of severe weakness was significantly higher in the pediatric group (63.6% vs. 36.4%; P = 0.008). Myalgia was significantly more frequent in adults (49.3% vs. 20.8%; P = 0.03). The median serum creatine kinase (CK) concentration was significantly higher in the pediatric group (7263.0 vs. 3388.5U/L; P = 0.03). Magnetic resonance imaging of the thigh revealed muscle edema in 82.8% of patients and fatty infiltration in 60.9%. Muscle edema scores in the sartorius (P = 0.02) and gracilis (P = 0.03) were significantly higher in the pediatric group. Fatty infiltration score was significantly correlated with disease duration (r = 0.51; P < 0.001). Dystrophic pathology was significantly more frequent in pediatric patients (47% vs. 8%; P = 0.001). Regeneration score was significantly higher in pediatric group (P = 0.025). Sarcolemmal deposition of membrane attack complex (MAC) was significantly greater in pediatric patients (P = 0.010) and correlated significantly with manual muscle testing-8 score (r = - 0.14; P = 0.04) and serum CK concentration (r = 0.36; P = 0.002). Pediatric patients presented with more severe weakness, higher CK concentration, higher muscle edema score in the sartorius and gracilis, more muscle regeneration, more sarcolemmal MAC deposition, and dystrophic pathology. Adult patients exhibited more myalgia and more minimal changes. Sarcolemmal MAC deposition is a biomarker for disease activity.

References

Schmidt J . Current Classification and Management of Inflammatory Myopathies. J Neuromuscul Dis. 2018; 5(2):109-129. PMC: 6004913. DOI: 10.3233/JND-180308. View

Mariampillai K, Granger B, Amelin D, Guiguet M, Hachulla E, Maurier F . Development of a New Classification System for Idiopathic Inflammatory Myopathies Based on Clinical Manifestations and Myositis-Specific Autoantibodies. JAMA Neurol. 2018; 75(12):1528-1537. PMC: 6583199. DOI: 10.1001/jamaneurol.2018.2598. View

Lim J, Rietveld A, De Bleecker J, Badrising U, Saris C, van der Kooi A . Seronegative patients form a distinctive subgroup of immune-mediated necrotizing myopathy. Neurol Neuroimmunol Neuroinflamm. 2018; 6(1):e513. PMC: 6192692. DOI: 10.1212/NXI.0000000000000513. View

Allenbach Y, Mammen A, Benveniste O, Stenzel W . 224th ENMC International Workshop:: Clinico-sero-pathological classification of immune-mediated necrotizing myopathies Zandvoort, The Netherlands, 14-16 October 2016. Neuromuscul Disord. 2017; 28(1):87-99. DOI: 10.1016/j.nmd.2017.09.016. View

Landon-Cardinal O, Koumako C, Hardouin G, Granger B, Reyngoudt H, Boisserie J . Severe axial and pelvifemoral muscle damage in immune-mediated necrotizing myopathy evaluated by whole-body MRI. Semin Arthritis Rheum. 2020; 50(6):1437-1440. DOI: 10.1016/j.semarthrit.2020.02.009. View

Pinal-Fernandez I, Casal-Dominguez M, Carrino J, Lahouti A, Basharat P, Albayda J . Thigh muscle MRI in immune-mediated necrotising myopathy: extensive oedema, early muscle damage and role of anti-SRP autoantibodies as a marker of severity. Ann Rheum Dis. 2016; 76(4):681-687. PMC: 6019551. DOI: 10.1136/annrheumdis-2016-210198. View

Fionda L, Lauletta A, Leonardi L, Alonso Perez J, Morino S, Merlonghi G . Muscle MRI in immune-mediated necrotizing myopathy (IMNM): implications for clinical management and treatment strategies. J Neurol. 2022; 270(2):960-974. PMC: 9886642. DOI: 10.1007/s00415-022-11447-7. View

Merlonghi G, Antonini G, Garibaldi M . Immune-mediated necrotizing myopathy (IMNM): A myopathological challenge. Autoimmun Rev. 2021; 21(2):102993. DOI: 10.1016/j.autrev.2021.102993. View

Liang W, Uruha A, Suzuki S, Murakami N, Takeshita E, Chen W . Pediatric necrotizing myopathy associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies. Rheumatology (Oxford). 2016; 56(2):287-293. PMC: 5410926. DOI: 10.1093/rheumatology/kew386. View

10.

Tansley S, Betteridge Z, Simou S, Jacques T, Pilkington C, Wood M . Anti-HMGCR Autoantibodies in Juvenile Idiopathic Inflammatory Myopathies Identify a Rare but Clinically Important Subset of Patients. J Rheumatol. 2017; 44(4):488-492. DOI: 10.3899/jrheum.160871. View

11.

Sener S, Batu E, Sari S, Kasap Cuceoglu M, Yildiz A, Talim B . A Child with Refractory and Relapsing Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Myopathy: Case-Based Review. J Neuromuscul Dis. 2023; 10(2):279-291. DOI: 10.3233/JND-221557. View

12.

Watanuki K, Koga H . Case report: Diagnostic clues for anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase myopathy in pediatric patients. Front Pediatr. 2023; 11:1102539. PMC: 10040642. DOI: 10.3389/fped.2023.1102539. View

13.

Wang C, Liang W . Pediatric immune-mediated necrotizing myopathy. Front Neurol. 2023; 14:1123380. PMC: 10067916. DOI: 10.3389/fneur.2023.1123380. View

14.

Lundberg I, Tjarnlund A, Bottai M, Werth V, Pilkington C, de Visser M . 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis. 2017; 76(12):1955-1964. PMC: 5736307. DOI: 10.1136/annrheumdis-2017-211468. View

15.

Morrow J, Matthews E, Raja Rayan D, Fischmann A, Sinclair C, Reilly M . Muscle MRI reveals distinct abnormalities in genetically proven non-dystrophic myotonias. Neuromuscul Disord. 2013; 23(8):637-46. PMC: 3744809. DOI: 10.1016/j.nmd.2013.05.001. View

16.

Mercuri E, Cini C, Pichiecchio A, Allsop J, Counsell S, Zolkipli Z . Muscle magnetic resonance imaging in patients with congenital muscular dystrophy and Ullrich phenotype. Neuromuscul Disord. 2003; 13(7-8):554-8. DOI: 10.1016/s0960-8966(03)00091-9. View

17.

Fischer D, Walter M, Kesper K, Petersen J, Aurino S, Nigro V . Diagnostic value of muscle MRI in differentiating LGMD2I from other LGMDs. J Neurol. 2005; 252(5):538-47. DOI: 10.1007/s00415-005-0684-4. View

18.

Yang M, Ji S, Xu L, Zhang Q, Li Y, Gao H . The Clinicopathological Distinction between Immune-Mediated Necrotizing Myopathy and Limb-Girdle Muscular Dystrophy R2: Key Points to Prevent Misdiagnosis. J Clin Med. 2022; 11(21). PMC: 9655252. DOI: 10.3390/jcm11216566. View

19.

Akoglu H . User's guide to correlation coefficients. Turk J Emerg Med. 2018; 18(3):91-93. PMC: 6107969. DOI: 10.1016/j.tjem.2018.08.001. View

20.

Hou Y, Shao K, Yan Y, Dai T, Li W, Zhao Y . Anti-HMGCR myopathy overlaps with dermatomyositis-like rash: a distinct subtype of idiopathic inflammatory myopathy. J Neurol. 2021; 269(1):280-293. DOI: 10.1007/s00415-021-10621-7. View