Anti–3‐hydroxy‐3‐methylglutaryl‐coenzyme a reductase autoantibody‐positive necrotizing autoimmune myopathy with dermatomyositis‐like eruption

A 47 year-old man presented with a 4-week history of myalgia, dysarthria, dysphagia, and generalized weakness after having been receiving atorvastatin for 1 year. On examination, he had a heliotrope rash and nonpruritic, erythematous macular rashes that were present around the neck, upper chest, and extensor surfaces of the interphalangeal and metacarpophalangeal joints. No nail findings such as telangiectasia or ragged cuticles were seen. Neurological examination revealed flaccid dysarthria associated with palatal weakness and mild weakness in the orbicularis oculi and orbicularis oris muscles. Motor strength was graded as follows (Medical Research Council [MRC] scale): neck flexors, 3; neck extensors, 4; shoulder abductors, 4; elbow flexors, 4; elbow extensors, 5; wrist extensors, 3; wrist flexors, 4; finger extensors, 3; first dorsal interossei, 2; hip flexors, 4; knee extensors, 4; knee flexors, 4; ankle dorsiflexors, 3; and plantar flexors, 4. Creatine kinase (CK) was elevated, with a peak level of 37,527 U/L (normal range, 30–220 U/L). Needle electromyography showed short-duration and smallamplitude motor unit potentials, fibrillation potentials, and positive-wave discharges in the proximal and distal limb muscles. Serum testing for the autoantibodies Jo-1, PM-SCL, SRP, and NXP2 were negative. A right rectus femoris muscle biopsy revealed muscle fiber size variability, mild fiber necrosis, and mild mononuclear infiltration without perifascicular atrophy. C5b9 staining for membrane attack complex was unremarkable, and major histocompatibility complex class I staining revealed a diffuse sarcolemmal overexpression (Fig. 1). A request for a biopsy of a distal limb muscle with greater weakness was declined by the patient. Serum anti-3-hydroxy-3methylglutaryl-coenzyme A reductase (anti-HMGCR) antibody exceeded 200 units (normal 20 units) on enzyme-linked immunosorbent assay (RDL Reference Laboratory, Los Angles, CA) and was also positive by immunoprecipitation by our own laboratory, confirming the diagnosis of statin-associated necrotizing autoimmune myopathy (NAM). Treatment was initiated with intravenous methylprednisolone 1 g per day for 5 days, followed by intravenous immunoglobulin (IVIG) 0.4 g/ kg/day for 5 days and oral prednisone 80 mg per day. However, muscle weakness persisted, and CK remained highly elevated in the range of 19,000 to 34,000 U/L. Subsequent treatment with plasmapheresis for 5 sessions led to a reduction of CK level to 6,481 U/L. The patient’s muscle strength returned to normal in all muscles except for the neck flexors, shoulder abductors, wrist extensors, and ankle dorsiflexors, which were graded as MRC 4. Maintenance plasmapheresis 2 days per month was continued. Mycophenolate mofetil was initiated at 1,000 mg twice per day, and prednisone dose was tapered down to 20 mg per day over the next 4 months. At month 5, the heliotrope and other skin rashes had resolved with a near complete recovery of limb strength and a CK level of 1,427 U/L. NAM can be a rare complication of statin usage that is associated with anti-HMGCR antibodies and is characterized by histopathological features of muscle fiber necrosis with minimal to no inflammation. Patients typically present with various degrees of symmetrical proximal limb weakness and prominent CK elevation that often exceeds 6,000 U/L. Treatment usually consists of corticosteroids, steroid sparing agents, or IVIG. Most patients require combination therapy and do not respond to corticosteroids alone. The history of statin use, prominent CK elevation, muscle fiber necrosis with minimal inflammation, and high-titer anti-HMGCR antibodies confirmed the diagnosis of anti-HMGCR associated NAM in our patient. Our patient showed a heliotrope rash and Gottron’s sign, cutaneous manifestations that are considered pathognomonic for dermatomyositis. Typical histopathologic features of dermatomyosistis such as perifascicular atrophy and prominent inflammation were not observed. Although anti-HMGCR antibody was not detected in 33 adult cases of dermatomyositis, it has been found in rare cases (0.8%) of juvenile dermatomyositis. Our case report raises the possibility of anti-HMGCR myopathy presenting with dermatomyositis-like features in adult patients. Recently, Lavian et al. described a patient who developed anti-HMGCR antibody-positive NAM with