20PRituximab in treatment-refractory childhood-onset immune-mediated necrotizing myopathy: a case series

Abstract

IMNM is a rare and severe autoimmune myopathy, recognized as one of the most disabling forms of inflammatory muscle disease. Several case reports have described a slowly progressive clinical course, occasionally mimicking muscular dystrophy. The ENMC has recommended rituximab (RTX) as a second-line therapeutic option for IMNM. However, this recommendation is based on limited evidence derived from a single case series involving eight patients. In this report, we describe two pediatric-onset, treatment-refractory cases of IMNM in which rituximab was initiated following inadequate response to prolonged immunosuppressive therapy. A 17-year-old girl presented with tetraplegia. Her symptoms began at age 7 with difficulty climbing stairs, frequent falls, and inability to rise from a seated position. She was misdiagnosed with muscular dystrophy for many years before being referred to our hospital. Her weakness had progressed to the point where she could no longer walk independently. She had no dysphagia or skin rash. On examination, she showed prominent proximal muscle weakness (MRC 3/5), neck flexors weaker than extensors, and no sensory deficits. Her mRS score was 3. Anti-HMGCR antibodies were positive; anti-SRP was negative. Muscle biopsy revealed features consistent with IMNM with some fatty replacement. MRI showed symmetrical muscle edema in both upper and lower limbs. She was diagnosed with childhood-onset IMNM mimicking muscular dystrophy. Initial treatment with corticosteroids (1 mg/kg) and mycophenolate mofetil led to reduced but persistently elevated CPK levels and no significant clinical improvement after one year. RTX was then initiated (1 cycle of 1000 mg, two weeks apart). Following treatment, she regained the ability to walk independently, though she remained unable to climb stairs, and CPK levels remained stable. An 18-year-old female presented with progressive limb weakness. She reported mild lower limb weakness beginning five years prior, which gradually worsened. In the past 6–8 months, the weakness progressed more rapidly, particularly affecting her ability to climb stairs. She had no joint pain, skin changes, dysphagia, or family history of neuromuscular disease. Neurological examination revealed proximal muscle weakness (MRC 3/5), with neck flexors weaker than extensors, and no sensory deficits or cranial nerve involvement. Her mRS score was 3. Autoantibody testing was negative for anti-HMGCR and anti-SRP, but anti-Mi-2α was strongly positive. Due to this antibody profile being atypical for the clinical presentation, a muscle biopsy was performed, confirming a diagnosis of IMNM. MRI showed a diffuse, symmetric muscle edema with fatty replacement of the posterior thigh. Initial treatment with corticosteroids and azathioprine failed to halt disease progression, and serum CPK remained elevated. RTX was given as in Case 1. Following treatment, while the mRS score remained unchanged, disease progression stabilized, CPK levels decreased significantly and remained stable. In both cases, RTX stabilized disease activity and CPK levels, despite minimal changes in functional scores. Delayed diagnosis (5–10 years from symptom onset) and significant fatty replacement seen on imaging and biopsy likely limited treatment response. These findings highlight the importance of early recognition and prompt aggressive therapy to prevent irreversible muscle damage in IMNM.