The patient was a 13-year-old Japanese boy, the first of three siblings from non-consanguineous parents. He had no history of statin exposure and no family history of neuromuscular disease. He was a basketball player and presented with progressive difficulties in shooting, running, and subsequently walking during the previous one month.
Vital signs were normal (heart rate, 82 beats/min; respiratory rate, 15 breaths/min; blood pressure, 113/57 mmHg; body temperature, 36.5 C). Physical examination revealed grade 3/5 muscle weakness in the upper extremities and 4/5 in the lower extremities based on the Medical Research Council (MRC) scale (0-5). The patient also presented with generalized erythematous skin rash (Figure 1). Other general physical examination findings were unremarkable.
Serum levels of CK (19,306 U/L), aldolase (257 U/L), aspartate aminotransferase (274 U/L), and lactate dehydrogenase (1,471 U/L) were all elevated. Magnetic resonance imaging detected signal hyperintensity on T2-weighted imaging and short tau inversion recovery imaging for muscles in the proximal upper and lower extremities (Figure 2). Muscle biopsy showed necrosis and regeneration of muscle fibers (Figure 3). Immunohistochemistry demonstrated overexpression of major histocompatibility complex class 1 and membrane attack complex (C5b-9) on the sarcolemma and granular sarcoplasmic expression of p62 (Figure 3). As measured by quantitative enzyme-linked immunosorbent assay (Cosmic Corporation, Tokyo, Japan), anti-HMGCR antibody level was 2.9 IU/ml (reference value <1.0 IU/ml), while negative results were obtained for anti-signal recognition particle antibody and other myositis-associated antibodies, including anti-Jo-1, anti-Mi-2, anti-MDA-5, and anti-TIF-1 gamma antibodies. The patient was subsequently diagnosed with anti-HMGCR myopathy.
Based on the consensus statement on the initial treatment for anti-HMGCR myopathy from the 224th European Neuromuscular Centre International Workshop, intravenous methylprednisolone (1 g/day for 3 days) followed by oral prednisolone (1 mg/kg/day), monthly IVIg (2 g/kg/dose, three times), and oral methotrexate (0.3 mg/kg/week) was started 3 months after the first evaluation. MRC scale scores for the upper and lower extremities normalized (grade 5/5) and serum CK (201 U/L), aldolase (8 U/L), aspartate aminotransferase (16 U/L), and lactate dehydrogenase (280 U/L) levels were all decreased by 3 months after treatment initiation. The patient resumed playing basketball at the same level as that before the onset of anti-HMGCR myopathy. The patient has continued to receive methotrexate monotherapy and as of the time of writing, has remained relapse-free for 2 years.