Case 1

A 61-year-old Indian man was re-referred to the neuromuscular clinic after a recurrence of proximal muscle weakness and myalgia. He had been referred 6 years earlier with myalgia and proximal muscle weakness that had worsened over 18 months. He had taken simvastatin 20 mg for over 2 years. His serum creatine kinase (CK) was elevated at 5000 IU/L (24–195). A subsequent muscle biopsy showed non-specific myopathic changes. After stopping the simvastatin, the symptoms completely resolved and his CK normalised.

Four years later, his primary care physician started him on atorvastatin 20 mg for recurrence of hypercholesterolaemia. A few weeks later his muscle symptoms recurred, noting difficulties with stairs and getting up from the ground after praying at the temple. Examination confirmed proximal muscle weakness in upper and lower limbs and a myopathic gait, prompting re-referral to our service. We stopped his statin, but unlike with his previous presentation, the weakness continued to progress. Serum CK was again elevated at 8100 IU/L. He was found to have 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies but testing for other myositis antibodies was negative. An MR scan of the lower limb muscles showed widespread oedema that was more pronounced posteriorly (figure 1A,B). A muscle biopsy showed scattered necrotic and regenerating fibres with no significant inflammation. Given the clinical context and the presence of detectable HMGCR antibodies, the features were consistent with an immune-mediated necrotising myopathy. We gave intravenous methylprednisolone followed by oral prednisolone 50 mg. We later started methotrexate as a corticosteroid sparing agent and established a weaning plan for prednisolone. Screening for underlying malignancy was negative.

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Figure 1

(A) Short tau inversion recovery axial MRI sequences at the level of the mid femur, showing muscle oedema affecting the hamstring muscles of semimembranosus, semitendinosus, biceps femoris and adductor magnus with subtle oedema in the quadriceps muscle group bilaterally. Note the relative sparing of sartorius and adductor longus. (B) Short tau inversion recovery axial MRI sequences at the level of the proximal tibia showing marked bilateral medial and lateral gastrocnemius muscle oedema.  AD, adductor magnus and longus; BFL, biceps femoris long head; GR, gracilis; LG, lateral gastrocnemius; MG, medial gastrocnemius; RF, rectus femoris; SA, sartorius; ST, semitendinosus; SM, semimembranosus; SOL, soleus; TA, tibialis anterior; TP, tibialis posterior; VL, vastus lateralis; VI, vastus intermedius; VM, vastus medialis.

Case 2

A 52-year-old Indian man was referred from rheumatology to the neuromuscular clinic with a 2-month history of dysphagia, weight loss, myalgia, as well as difficulties getting out of a chair and managing stairs. He had taken simvastatin 20 mg for over 10 years and the dose had increased to 40 mg 12 months before. Examination confirmed symmetrical proximal weakness in his upper and lower limbs. Serum CK was elevated at 11 000 IU/L (24–195). CT scan of chest, abdomen and pelvis, upper gastrointestinal endoscopy and colonoscopy were normal, although a barium swallow did identify oesophageal dysmotility. MR scan of his lower limb muscles showed widespread oedema while electromyography showed myopathic changes with evidence of irritability. He had detectable HMGCR antibodies but no other myositis-specific antibodies. The muscle biopsy findings were consistent with an immune-mediated necrotising myopathy (figure 2A,B). After stopping the statin, his symptoms markedly improved. His swallowing improved and weight started to increase. He could walk for half a mile on a flat surface and could manage two or three flights of stairs. Two months later, there was only mild weakness in his deltoid muscles and he could perform a squat and get up from the floor without difficulty. His serum CK was 2700 IU/L but he continued to improve without treatment and felt almost 100% back to normal.

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Figure 2

(A) H&E stained section showing scattered fibres at various stages of necrosis and regeneration (pale, purple, sometimes vacuolated fibres). Secondary changes (increase in variability of fibre diameters and internal nuclei are also seen). Note the relative lack of inflammatory cells, which are mostly restricted to necrotic fibres. (B) Acid phosphatase highlighting various stages of myophagocytosis in necrotic fibres (red staining).

Case 3

A 46-year-old woman presented with a 1-year history of difficulty climbing stairs, getting up from the floor while at work, and weakness in her arms. She had been previously well and had never taken a statin. She was referred to a rheumatologist. Her serum CK was raised at 3800 IU/L (24–170) and electromyography showed myopathic changes with evidence of irritability. MR scan of the lower limb muscles showed oedema, suggesting bilateral myositis. She was started on prednisolone 40 mg once a day. A muscle biopsy showed features consistent with an immune-mediated necrotising myopathy. Testing for myositis antibodies was negative although HMGCR antibodies were subsequently identified. Although her serum CK fell to 1000 IU/L over a few weeks, her limb weakness continued to progress despite a course of intravenous methylprednisolone. She was subsequently referred to us for a second opinion. Gradually, the oral prednisolone was reduced and methotrexate introduced as a corticosteroid sparing agent. She later developed sensory symptoms and was found to have an underlying small-fibre neuropathy that has been treated symptomatically.