Statins and Immune-Mediated Necrotizing Myopathy

Abstract

Statins are a well-recognized cause of a variety of skeletal myopathic effects, which generally resolve when discontinuing the treatment. Among autoimmune manifestations associated with statins, there is immune-mediated necrotizing myopathy (IMNM).The present article summarizes the main features of statin-related IMNM, describing diagnosis, classification, epidemiology, treatment, and the main autoantibodies detected.Statins are a well-recognized cause of a variety of skeletal myopathic effects, which generally resolve when discontinuing the treatment. Among autoimmune manifestations associated with statins, there is immune-mediated necrotizing myopathy (IMNM).The present article summarizes the main features of statin-related IMNM, describing diagnosis, classification, epidemiology, treatment, and the main autoantibodies detected.Although it is impossible to define the precise number, it evident that more than 550 statin-related IMNM cases have been described in the literature. Among IMNM, two forms must be distinguished: with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and with anti-signal recognition particle (SRP) antibodies. The differential diagnosis should be made between the IMNM and self-limited statin-related myopathy, drug-induced rhabdomyolysis, and nonautoimmune myopathies.Patients who have failed to normalize high creatine phosphokinase (CPK) after statin withdrawal should be tested for anti-HMGCR antibodies and, if these are positive, undergo muscle biopsy to confirm the diagnosis of IMNM. Pharmacological therapy of IMNM, not yet based on evidence, involves the use of high-dose corticosteroids, immunosuppressant drugs used alone or in combination, intravenous immunoglobulins (IVIg) or plasmapheresis.

Atypical presentation of necrotising autoimmune myopathy

“…The common presentation of NAM is proximal muscle weakness and myalgia. Atypical presentations are relatively rare and include dysphagia (as in our patient), Raynaud’s phenomenon and interstitial lung disease 1 3. Symmetrical limb weakness in patients with anti-HMGCR antibody can develop acutely like in our patient or can be subacute to chronic.…”

“…Genetic susceptibility and other unknown factors may also play a role, as not all patients taking a statin develop NAM 6. Unlike other statin-associated myopathies, NAM usually persists after discontinuation of statin or as in the present case, may present after discontinuation of statin 3. When onset follows discontinuation of statins, symptom onset has been reported 0.5 to 20 months following discontinuation of statin,1 7 which is similar to our patient who developed symptoms 13 months after stopping atorvastatin due to elevation in liver enzymes.…”

“…Idiopathic inflammatory myopathies (IIM) are heterogeneous acquired muscle diseases characterised by proximal muscle weakness, elevated muscle enzymes, irritable myopathy on EMG and characteristic histopathological features. IIM is currently classified into five main types based on the clinical and phenotype specific autoantibody group; dermatomyositis, polymyositis, inclusion body myositis, overlap myositis and NAM 3 4…”

“…Necrotising autoimmune myopathy (NAM) is a rare form of idiopathic inflammatory myopathy 1 2. Statin-associated NAM, a subtype has only been described in the literature in about 550 cases with an estimated incidence of two to three cases in 1 000 000 patients exposed to statins per year 3. We describe a case of statin-associated NAM presenting as severe oropharyngeal dysphagia and acutely progressing to severe symmetrical muscle weakness while receiving treatment with high-dose corticosteroids.…”

Polymyositis, Dermatomyositis, and Statins: A Review

“…Anti-HMGCR antibodies were dosed in a total of 9 patients: those described in the myopathy). It is associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies (anti-HMGCR) [59].…”