Highlights
- •In northern Spain, anti-HMGCR IMNM usually affects people over 50 years with exposure to statins.
- •We confirm that HLA-DRB1×11 is associated with an increased risk of anti-HMGCR IMNM in Spain.
- •The SLCO1B1 gene does not seem to play a role in the anti-HMGCR IMNM genetic network.
- •Vitamin D deficiency and hypothyroidism might be predisposing factors for anti-HMGCR IMNM.
Abstract
Objective
To characterize the demographic, genetic, clinical, and serological features of patients
with anti-3‑hydroxy-3-methylglutaryl-CoA reductase (HMGCR) immune-mediated necrotizing
myopathy (IMNM) in a region of northern Spain.
Methods
Study of all patients diagnosed with anti-HMGCR IMNM during a 5-year period at a reference
hospital in northern Spain. Besides clinical and laboratory data, we analyzed the
genetic influence of HLA genes and the rs4149056 (c.521T>C) single nucleotide polymorphism
(SNP) in the SLCO1B1 gene.
Results
8 patients (5 women, 3 men) with a mean ± SD age of 64.9 ± 7.3 years, fulfilled the
criteria for anti-HMGCR IMNM. The incidence rate was 0.6 per 100.000 person-years
and the prevalence 3 per 100.000 population. All patients had been exposed to statins.
All of them had predominant lower limb proximal and symmetric muscle weakness that
was severe in 2 and had elevated serum CK levels with a median [IQR] of 4488 [2538–9194]
IU/L. Serum 25‑hydroxy vitamin D levels were decreased in all patients in whom it
was determined. The 3 patients with a previous diagnosis of hypothyroidism had abnormal
levels of TSH at the time of diagnosis. All patients experienced improvement with
different schemes of immunosuppressive therapy. Noteworthy, 7 of 8 patients carried
the HLA-DRB1*11 allele. The frequency of the rs4149056 C allele in the SLCO1B1 gene (12.5%) was similar to that of the general population.
Conclusion
In northern Spain, anti-HMGCR IMNM preferentially affects people over 50 years of
age who are carriers of the HLA-DRB1*11 allele and take statins. Both low vitamin D levels and hypothyroidism may play a
potential predisposing role in the development of this disease.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to European Journal of Internal MedicineAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Immune-mediated necrotizing myopathy: clinical features and pathogenesis.Nat Rev Rheumatol. 2020; 16: 689-701
- Inflammatory myopathies: update on diagnosis, pathogenesis and therapies, and COVID-19-related implications.Acta Myol. 2020; 39: 289-301
- Increasing incidence of immune-mediated necrotizing myopathy: single-centre experience.Rheumatology (Oxford). 2015; 54: 2010-2014
- Anti-HMGCR antibodies as a biomarker for immune-mediated necrotizing myopathies: a history of statins and experience from a large international multi-center study.Autoimmun Rev. 2016; 15: 983-993
- Anti-HMGCR antibodies demonstrate high diagnostic value in the diagnosis of immune-mediated necrotizing myopathy following statin exposure.Immunol Res. 2017; 65: 276-281
- Statin-induced myalgia and myositis: an update on pathogenesis and clinical recommendations.Expert Rev Clin Immunol. 2018; 14: 215-224
- Increased frequency of DRB1×11:01 in anti-hydroxymethylglutaryl-coenzyme A reductase-associated autoimmune myopathy.Arthritis Care Res (Hoboken). 2012; 64: 1233-1237
- Clinical and genetic associations of autoantibodies to 3-hydroxy-3-methyl-glutaryl-coenzyme a reductase in patients with immune-mediated myositis and necrotizing myopathy.Muscle Nerve. 2015; 52: 196-203
- SLCO1B1 variants and statin-induced myopathy–a genomewide study.N Engl J Med. 2008; 359: 789-799
- Genomewide association study of statin-induced myopathy in patients recruited using the UK clinical practice research datalink.Clin Pharmacol Ther. 2019; 106: 1353-1361
- Pharmacogenetics of Statin-Induced Myotoxicity.Front Genet. 2020; 11575678
- Immune-mediated necrotizing myopathies working group. 224th ENMC international workshop: Clinico-sero-pathological classification of immune-mediated necrotizing myopathies Zandvoort, The Netherlands, 14-16 October 2016.Neuromuscul Disord. 2018; 28: 87-99
- Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy.Arthritis Rheum. 2011; 63: 713-721
- Anti-HMGCR autoantibodies in European patients with autoimmune necrotizing myopathies: inconstant exposure to statin.Medicine (Baltimore). 2014; 93: 150-157
- Clinical features and treatment outcomes of necrotizing autoimmune myopathy.JAMA Neurol. 2015; 72: 996-1003
- Statin-associated autoimmune myopathy: a distinct new IFL pattern can increase the rate of HMGCR antibody detection by clinical laboratories.Autoimmune Rev. 2016; 15: 1161-1166
- Clinical features and prognosis in anti-SRP and anti-HMGCR necrotising myopathy.J Neurol Neurosurg Psychiatry. 2016; 87: 1038-1044
- Treatment and outcomes in necrotising autoimmune myopathy: an Australian perspective.Neuromuscul Disord. 2016; 26: 734-740
- Atorvastatin-induced necrotizing autoimmune myositis.Medicine (Baltimore). 2017; 96: e5694
- Statin-induced anti-HMGCR myopathy: successful therapeutic strategies for corticosteroid-free remission in 55 patients.Arthritis Res Ther. 2020; 22: 5
- Clinico-serologic features of statin-induced necrotising autoimmune myopathy in a single-centre cohort.Clin Rheumatol. 2018; 37: 543-547
Article info
Publication history
Published online: April 26, 2022
Accepted:
April 12,
2022
Received in revised form:
April 9,
2022
Received:
January 20,
2022
Identification
Copyright
© 2022 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
