APLAR Grand Round Blackboard

Question 1

A 50-year-old female patient with diabetes mellitus and ischemic heart disease was referred from the cardiology clinic with generalized myalgia for one month and raised creatinine phosphokinase (CPK) of 8752 IU/dl. The patient was given atorvastatin 40mg daily following an acute STEMI with primary PCI to LAD 8 months ago. Her serum TSH level was 3.120 mIU/l.

What is the most appropriate next step in management?

Your Answer is Incorrect

Answer with Detailed explanation

The correct answer is C. To withhold atorvastatin

A detailed explanation will be given after Question 2

Your Answer is Correct

Answer with Detailed explanation

A detailed explanation will be given after Question 2

Question 2

Despite stopping atorvastatin, her symptoms persisted, and the CPK remained elevated. Clinical examination revealed proximal myopathy. EMG showed fibrillations and a brief duration of simple and complex motor unit potentials. A muscle biopsy was performed which revealed necrotic fibres with macrophage infiltration.

What is the diagnosis?

Your Answer is Incorrect

Answer with Detailed explanation

The correct answer is C. Statin-induced immune-mediated necrotizing myositis

A spectrum of statin-induced myotoxicity is defined, ranging from asymptomatic CPK elevations to myalgia or weakness with a raised CPK level, to rhabdomyolysis and myositis with biopsy-proven muscle inflammation.

Alfirevic et al published a 6-stage classification of statin-related myotoxicity which provides a useful algorithm to differentiate these stages and to guide the investigation.

The most severe form in the spectrum, the immune-mediated necrotizing myositis, is a very rare disorder with an annual incidence of 2 patients per million population and clinically resembles polymyositis. The more common milder spectrum of cases of statin-induced myotoxicity resolve with the withdrawal of the statin.

EMG, muscle MRI scan and muscle biopsy will help diagnose statin-induced autoimmune necrotizing myopathy. A muscle biopsy demonstrates a necrotic rather than an inflammatory picture.

Identifying anti-HMGCR antibodies supports the diagnosis of statin-induced necrotizing myositis in the correct clinical settings with high sensitivity and specificity. It is strongly associated with the HLA-DRB1*1101 gene.

Around one-third of patients with anti-HMGCR-positive immune-mediated necrotizing myositis are not exposed to statin before, and those patients are characteristically younger with higher levels of inflammation.

Therapeutic guidelines based on evidence-based medicine are lacking for this condition. However, steroid alone may not be adequate for treatment. These patients may need a combination of DMARDs and intravenous immunoglobulin.

Reference

1. Mammen A. L. Statin-associated autoimmune myopathy. New England Journal of Medicine. 2016;374(7):664–669. doi: 10.1056/nejmra1515161.
2. Alfirevic A, Neely D, Armitage J, et al. Phenotype standardization for statin-induced myotoxicity. Clin Pharmacol Ther. 2014;96:470–476.
3. Selva-O'Callaghan A, et al Statin-induced myalgia and myositis: an update on pathogenesis and clinical recommendations. Expert Rev Clin Immunol. 2018 Mar; 14(3):215-224. doi: 10.1080/1744666X.2018.1440206.

By Dr Amal Sithira Thilakarathne, Consultant in Rheumatology & Rehabilitation, District General hospital, Matale, Sri Lanka

Your Answer is Correct

Answer with Detailed explanation

A spectrum of statin-induced myotoxicity is defined, ranging from asymptomatic CPK elevations to myalgia or weakness with a raised CPK level, to rhabdomyolysis and myositis with biopsy-proven muscle inflammation.

Alfirevic et al published a 6-stage classification of statin-related myotoxicity which provides a useful algorithm to differentiate these stages and to guide the investigation.

The most severe form in the spectrum, the immune-mediated necrotizing myositis, is a very rare disorder with an annual incidence of 2 patients per million population and clinically resembles polymyositis. The more common milder spectrum of cases of statin-induced myotoxicity resolve with the withdrawal of the statin.

EMG, muscle MRI scan and muscle biopsy will help diagnose statin-induced autoimmune necrotizing myopathy. A muscle biopsy demonstrates a necrotic rather than an inflammatory picture.

Identifying anti-HMGCR antibodies supports the diagnosis of statin-induced necrotizing myositis in the correct clinical settings with high sensitivity and specificity. It is strongly associated with the HLA-DRB1*1101 gene.

Around one-third of patients with anti-HMGCR-positive immune-mediated necrotizing myositis are not exposed to statin before, and those patients are characteristically younger with higher levels of inflammation.

Therapeutic guidelines based on evidence-based medicine are lacking for this condition. However, steroid alone may not be adequate for treatment. These patients may need a combination of DMARDs and intravenous immunoglobulin.

Reference

1. Mammen A. L. Statin-associated autoimmune myopathy. New England Journal of Medicine. 2016;374(7):664–669. doi: 10.1056/nejmra1515161.
2. Alfirevic A, Neely D, Armitage J, et al. Phenotype standardization for statin-induced myotoxicity. Clin Pharmacol Ther. 2014;96:470–476.
3. Selva-O'Callaghan A, et al Statin-induced myalgia and myositis: an update on pathogenesis and clinical recommendations. Expert Rev Clin Immunol. 2018 Mar; 14(3):215-224. doi: 10.1080/1744666X.2018.1440206.

By Dr Amal Sithira Thilakarathne, Consultant in Rheumatology & Rehabilitation, District General hospital, Matale, Sri Lanka