Anti-Signal Recognition Particle Antibody-Positive Immune-Mediated Necrotizing Myopathy Diagnosed by Re-Evaluation 40 Years After Symptom Onset

Neuropathology. 2025 Dec;45(6):e70034. doi: 10.1111/neup.70034.

ABSTRACT

Immune-mediated necrotizing myopathy (IMNM) is a frequent subtype of idiopathic inflammatory myopathies. Distinguishing juvenile-onset IMNM from muscular dystrophy is often difficult, particularly when the disorder takes a chronic course. We describe a 45-year-old Japanese woman with progressive generalized weakness. Her early motor milestones were normal until age 4, but by 5 years she developed Gowers’ sign. At that time, she was noted to have proximal weakness, scapular winging, gait impairment, and markedly elevated serum creatine kinase (6069 IU/L). A biopsy of the left biceps brachii suggested muscular dystrophy. Her disease advanced, and she required a wheelchair during elementary school. At age 41 she was referred to the neurology department at Tottori University Hospital, and at 45 years she was re-evaluated. Examination revealed symmetric proximal weakness, atrophy, severe spinal deformity, and bilateral pes cavus. Electromyography demonstrated prominent myogenic changes, and muscle MRI disclosed profound atrophy with fatty replacement of proximal muscles. A repeat biopsy from the left tibialis anterior showed severe myofiber atrophy but no necrosis, regeneration, or inflammatory infiltration. Immunohistochemistry for dystrophy-associated proteins, MHC class I, and p62 was unremarkable. In contrast, retrospective review of the original biopsy revealed diffuse MHC class I expression and granular sarcoplasmic p62 staining, supporting a diagnosis of IMNM. Although ELISA results were negative, RNA immunoprecipitation identified anti-signal recognition particle antibodies. This patient illustrates an uncommon presentation of juvenile-onset IMNM that remained untreated for decades. The absence of characteristic histological features on biopsy performed 40 years after disease onset emphasizes the diagnostic challenges in long-standing cases. Careful reassessment of earlier tissue samples, in combination with extended antibody testing, may be essential for establishing the correct diagnosis in similar situations.

PMID:41239879 | DOI:10.1111/neup.70034