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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...

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Autores principales: Della Marina, Adela, Pawlitzki, Marc, Ruck, Tobias, van Baalen, Andreas, Vogt, Nadine, Schweiger, Bernd, Hertel, Swantje, Kölbel, Heike, Wiendl, Heinz, Preuße, Corinna, Roos, Andreas, Schara-Schmidt, Ulrike
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470706/
https://www.ncbi.nlm.nih.gov/pubmed/34572153
http://dx.doi.org/10.3390/children8090721
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author Della Marina, Adela
Pawlitzki, Marc
Ruck, Tobias
van Baalen, Andreas
Vogt, Nadine
Schweiger, Bernd
Hertel, Swantje
Kölbel, Heike
Wiendl, Heinz
Preuße, Corinna
Roos, Andreas
Schara-Schmidt, Ulrike
author_facet Della Marina, Adela
Pawlitzki, Marc
Ruck, Tobias
van Baalen, Andreas
Vogt, Nadine
Schweiger, Bernd
Hertel, Swantje
Kölbel, Heike
Wiendl, Heinz
Preuße, Corinna
Roos, Andreas
Schara-Schmidt, Ulrike
author_sort Della Marina, Adela
collection PubMed
description (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.
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spelling pubmed-84707062021-09-27 Clinical Course, Myopathology and Challenge of Therapeutic Intervention in Pediatric Patients with Autoimmune-Mediated Necrotizing Myopathy Della Marina, Adela Pawlitzki, Marc Ruck, Tobias van Baalen, Andreas Vogt, Nadine Schweiger, Bernd Hertel, Swantje Kölbel, Heike Wiendl, Heinz Preuße, Corinna Roos, Andreas Schara-Schmidt, Ulrike Children (Basel) Article (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. MDPI 2021-08-24 /pmc/articles/PMC8470706/ /pubmed/34572153 http://dx.doi.org/10.3390/children8090721 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Della Marina, Adela
Pawlitzki, Marc
Ruck, Tobias
van Baalen, Andreas
Vogt, Nadine
Schweiger, Bernd
Hertel, Swantje
Kölbel, Heike
Wiendl, Heinz
Preuße, Corinna
Roos, Andreas
Schara-Schmidt, Ulrike
Clinical Course, Myopathology and Challenge of Therapeutic Intervention in Pediatric Patients with Autoimmune-Mediated Necrotizing Myopathy
title Clinical Course, Myopathology and Challenge of Therapeutic Intervention in Pediatric Patients with Autoimmune-Mediated Necrotizing Myopathy
title_full Clinical Course, Myopathology and Challenge of Therapeutic Intervention in Pediatric Patients with Autoimmune-Mediated Necrotizing Myopathy
title_fullStr Clinical Course, Myopathology and Challenge of Therapeutic Intervention in Pediatric Patients with Autoimmune-Mediated Necrotizing Myopathy
title_full_unstemmed Clinical Course, Myopathology and Challenge of Therapeutic Intervention in Pediatric Patients with Autoimmune-Mediated Necrotizing Myopathy
title_short Clinical Course, Myopathology and Challenge of Therapeutic Intervention in Pediatric Patients with Autoimmune-Mediated Necrotizing Myopathy
title_sort clinical course, myopathology and challenge of therapeutic intervention in pediatric patients with autoimmune-mediated necrotizing myopathy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470706/
https://www.ncbi.nlm.nih.gov/pubmed/34572153
http://dx.doi.org/10.3390/children8090721
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