Clinical Course, Myopathology and Challenge of Therapeutic Intervention in Pediatric Patients with Autoimmune-Mediated Necrotizing Myopathy.

(1)

Background

Immune-mediated necrotizing myopathy (IMNM) is a rare form of inflammatory muscle disease which is even more rare in pediatric patients. To increase the knowledge of juvenile IMNM, we here present the clinical findings on long-term follow-up, myopathological changes, and therapeutic strategies in two juvenile patients. (2)

Methods

Investigations included phenotyping, determination of antibody status, microscopy on muscle biopsies, MRI, and response to therapeutic interventions. (3)

Results

Anti-signal recognition particle (anti-SRP54) and anti- 3-hydroxy-3-methylglutarly coenzyme A reductase (anti-HMGCR) antibodies (Ab) were detected in the patients. Limb girdle presentation, very high CK-levels, and a lack of skin rash at disease-manifestation and an absence of prominent inflammatory signs accompanied by an abnormal distribution of α-dystroglycan in muscle biopsies initially hinted toward a genetically caused muscle dystrophy. Further immunostaining studies revealed an increase of proteins involved in chaperone-assisted autophagy (CASA), a finding already described in adult IMNM-patients. Asymmetrical muscular weakness was present in the anti-SRP54 positive Ab patient. After initial stabilization under therapy with intravenous immunoglobulins and methotrexate, both patients experienced a worsening of their symptoms and despite further therapy escalation, developed a permanent reduction of their muscle strength and muscular atrophy. (4)

Conclusions

Diagnosis of juvenile IMNM might be complicated by asymmetric muscle weakness, lack of cutaneous features, absence of prominent inflammatory changes in the biopsy, and altered α-dystroglycan.