Ab1431 epidemiological and Genetic Features of Anti-3-Hydroxy-3-Methylglutaryl-Coa Reductase Necrotizing Myopathy in Northern Spain: Single-Center Experience

Abstract

BackgroundAnti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) immune-mediated necrotizing myopathy (IMNM) is an entity of growing interest. However, data on epidemiology and clinical spectrum are still scarce and there is a need for the identification of its potential risk factors.ObjectivesTo characterize the demographic, genetic, clinical, and serological features of patients with anti-HMGCR IMNM in a region of northern Spain.MethodsStudy 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.Results8 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 dyslipidemia and had been exposed to statins. Seven of the 8 of cases complained of myalgia. All of them had predominant lower limb proximal and symmetric muscle weakness that was severe in 2 of them. None of the patients had extra-muscular involvement. No evidence of malignancy was found. All patients 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.ConclusionIn northern Spain, the IMNM anti-HMGCR 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 diseaseTable 1.PatientAge/SexHLA DRB1*11rs4149056 genotypeMRC at the weakest muscle group*DysphagiaCK (IU/L) at diagnosisAnti-HMGCR titer (CU)Induction therapy*Maintenance therapyClinical improvement**CK (IU/L) at last follow-up visit156/MYesTT2No8963277.8GC. IVIG.MTXGC. IVIG. MTX. RTXMarked134269/FYesTT0Yes9271235.9GC iv bolus. IVIG.GC. MTX. RTX.Marked890364/FYesTT3No4000242.6IVIG.IVIG.RTXMarked1284479/MYesTT4No4977145.6GC. IVIG.GC. IVIG.Complete92562/FNoTT3No2116210.0GCGC.MTX.Marked236657/FYesTC4No2294259.3IGIVIGIVComplete235768/FYesTT3No3273236.0GC. IGIV. AZA.GC. AZAComplete249864/MYesTC4Yes11000179.0GC iv bolus. AZA.GC. AZAComplete161AZA: azathioprine; CK: creatinine kinase; CU: chemiluminescence units; F: female; GC: glucocorticoids; IVIG: intravenous immunoglobulins; M: male; MRC: medical research council scale; MTX: methotrexate; RTX: rituximab; ** Induction therapy initiated within 3 months of diagnosis. **Clinical improvement: no improvement (no improvement in MRC grade), mild improvement (improvement of MRC grade but still requiring assistance for activities of daily living), marked improvement (persistence of mild weakness without functional limitation), and complete improvement (return to baseline with no symptoms or signs of weakness).Disclosure of InterestsNone declared