Clinical Course, Myopathology and Challenge of Therapeutic Intervention in Pediatric Patients with Autoimmune-Mediated Necrotizing Myopathy
Adela Della Marina,
Marc Pawlitzki,
Tobias Ruck,
Andreas van Baalen,
Nadine Vogt,
Bernd Schweiger,
Swantje Hertel,
Heike Kölbel,
Heinz Wiendl,
Corinna Preuße,
Andreas Roos,
Ulrike Schara-Schmidt
Affiliations
Adela Della Marina
Centre for Neuromuscular Disorders and Centre for Translational Neuro- and Behavioral Sciences, Department of Pediatric Neurology University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
Marc Pawlitzki
Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital Münster, 48149 Münster, Germany
Tobias Ruck
Department of Neurology with Institute of Translational Neurology, University Hospital Münster, 48149 Münster, Germany
Andreas van Baalen
Clinic for Child and Adolescent Medicine II, University Hospital Schleswig-Holstein, 24105 Kiel, Germany
Nadine Vogt
Clinic for Child and Adolescent Medicine II, University Hospital Schleswig-Holstein, 24105 Kiel, Germany
Bernd Schweiger
Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
Swantje Hertel
Centre for Neuromuscular Disorders and Centre for Translational Neuro- and Behavioral Sciences, Department of Pediatric Neurology University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
Heike Kölbel
Centre for Neuromuscular Disorders and Centre for Translational Neuro- and Behavioral Sciences, Department of Pediatric Neurology University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
Heinz Wiendl
Department of Neurology with Institute of Translational Neurology, University Hospital Münster, 48149 Münster, Germany
Corinna Preuße
Department of Neuropathology, Humboldt-Universität zu Berlin and Berlin Institute of Health, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany
Andreas Roos
Centre for Neuromuscular Disorders and Centre for Translational Neuro- and Behavioral Sciences, Department of Pediatric Neurology University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
Ulrike Schara-Schmidt
Centre for Neuromuscular Disorders and Centre for Translational Neuro- and Behavioral Sciences, Department of Pediatric Neurology University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
(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.