A 4-year-old girl, the first child of nonconsanguineous parents, with normal motor development, presented with frequent falls, difficulty getting up from the floor, and muscle pain for several months. Her initial serum creatine kinase (CK) level was 820 U/L, and EMG showed a myopathic pattern. Echocardiogram and electrocardiogram were both normal. She was considered as having juvenile polymyositis by the pediatric rheumatologist, and treatment with prednisolone was initiated. At first, she presented with improvement and stabilization of signs and symptoms, but 5 months later, the weakness worsened rapidly, and she was restricted to a wheelchair, with a persistent elevated serum CK level (746 U/L). Muscle MRI showed diffuse, symmetrical, interstitial edema in the proximal and distal upper limb muscles and in glutei and thigh muscles, without fat infiltration or atrophy (figure). The diagnostic hypothesis of idiopathic inflammatory myopathy (IIM) was considered, and at the age of 5 years, she was referred to our service, with generalized weakness and severe axial involvement with loss of head control. A biceps brachii muscle biopsy was performed and showed severe dystrophic pattern, numerous necrotic fibers with macrophage reaction (CD68+ cells), lymphocyte endomysial infiltration (CD8+ cells), increased MHC-I expression, and intracytoplasmic aggregates (figure). The common antibodies for immune-mediated necrotizing myopathy (IMNM), anti-HMGCR and anti-SRP antibodies, were negative. As seronegative IMNM may occur and considering the intense edema in the muscle MRI and the significant macrophage reaction on the muscle biopsy, the possibility of inflammatory myopathy remained as the main clinical diagnosis. Monthly IV methylprednisolone and immunoglobulin were initiated and further associated with oral prednisolone and methotrexate, promoting improvement of head control and proximal weakness, and enabling her to achieve sitting ability. However, after 4 months of sustained response, she started getting worse again, becoming refractory to immunosuppressive treatment. At that time, mycophenolate mofetil and rituximab were added to treatment, but she did not respond.