10. Warning: statin-induced autoimmune necrotising myositis
Authors: Jasim Muhamad , Ibrahim Jafar , Scotton William , Manfredonia Francesco , Timmons Margaret , Sapkota Hem , Barkham Nick 
Published: September 2019

Abstract

Introduction
Statins are frequently prescribed, following or in order to prevent cardiovascular events. They inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoA), an enzyme involved in cholesterol synthesis. Up to 20% of patients experience myalgia which resolve after the drug is stopped. We highlight a more serious and potentially life-threatening complication: statin-induced autoimmune necrotising myositis (SIANM). Recently SIANM has been differentiated from inflammatory polymyositis. Patients present with bilateral proximal muscle weakness, elevated creatinine kinase, a muscle biopsy with necrosis and a positive HMGCoA reductase antibody. The latter has been found to be a specific and sensitive investigation for SIANM.

Case description
Given the rarity of SIANM, no guidelines available recommend a best course of treatment, here we highlight 3 successfully treated patients.
Case 1: 72-year-old man with hypercholesterolaemia, type 2 diabetes and hypertension presented with progressive proximal symmetrical weakness for 6 months. He started 20mg atorvastatin a year earlier and stopped this 2 months before admission. Examination revealed 4/5 muscle strength proximally in all 4 limbs and the patient struggled to stand from sitting. CK was elevated at 8223 IU/L (30-200). EMG confirmed a myopathic process and MRI thighs showed active inflammation. A muscle biopsy and HMGCoA antibodies confirmed SIANM and the patient commenced IV and then oral steroids. The patient deteriorated rapidly over the subsequent days with progressive weakness and dysphonia. He developed bilateral pneumonias and was admitted to ITU. Here we commenced the patient on IV immunoglobulin (IVIG) and rituximab. With this he improved significantly, with increasing power and a normalised CK.
Case 2: 55-year-old old man with a background of previous MI in 2013 (after which he commenced atorvastatin), type 2 diabetes, hypercholesterolemia and hypertension presented with progressive bilateral proximal muscle weakness. Serum CK found to be 8413, his statin was stopped and the patient underwent extensive investigation. Once again investigations confirmed the diagnosis of SIANM. The patient commenced steroid treatment but despite initial improvement in his power, this soon plateaued as did his CK. He was commenced on IVIG and methotrexate and found significant benefit with these treatments.
Case 3: 60-year-old lady presented with a 5-month history of generalised aches and pains with difficulty standing from sitting. She had been on atorvastatin for many years but her symptoms did not improve despite having stopped this 5 months previously. Investigations confirmed a SIANM. The patient was commenced on steroids and methotrexate with good effect.

Discussion
Patients presenting on statins with proximal symmetrical weakness and a raised CK should have HMGCOA antibodies checked as part of a myositis screen. Though statins should always be stopped, patients with SIANM can continue to deteriorate despite drug discontinuation and steroid treatment. Such patients should be considered for immunosuppression. The 3 cases described show positive response to a combination of methotrexate, IVIG and/or rituximab. This seems to mirror the growing clinical experience in other published case reports.

Key learning points
Patients presenting on statins with proximal symmetrical weakness and a raised CK should have HMGCOA antibodies checked as part of a myositis screen.
Withdrawal of the statin and steroid treatment alone is often insufficient to successfully treat SIANM.
Close monitoring of a patient’s power and CK levels are required even after withdrawal of a statin and treatment with steroid as patients can continue to deteriorate.
In such cases, additional treatment with methotrexate, IVIG and/ or rituximab appears to have the best outcomes.

Conflicts of interest
The authors have declared no conflicts of interest.