Cyril Gitiaux1, Marie De Antonio2, Jessie Aouizerate3, Romain K Gherardi4, Thomas Guilbert5, Christine Barnerias6, Christine Bodemer7, Karine Brochard-Payet8, Pierre Quartier9, Lucile Musset10, Bénédicte Chazaud5, Isabelle Desguerre11, Brigitte Bader-Meunier9. 1. Department of Pediatric Neurology and Pediatric Neurophysiology, Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, AP-HP, Referral Center for Neuromuscular Diseases 'Garches-Necker-Mondor-Hendaye', Créteil, INSERM U1016, Genetics and development, Institut Cochin, Paris-Descartes University, CNRS UMR 8104, Genetics and development, Institut Cochin, Paris-Descartes University, cyril.gitiaux@nck.aphp.fr. 2. Department of Pathology, AP-HP, Albert Chenevier-Henri Mondor Hospital, Créteil, INSERM UMRS1138-Team 22, Centre de Recherche des Cordeliers, Paris-Descartes University, UPMC University, Paris. 3. Department of Pathology, AP-HP, Albert Chenevier-Henri Mondor Hospital, Créteil. 4. Department of Pathology, AP-HP, Albert Chenevier-Henri Mondor Hospital, Créteil, INSERM U955-Team 10, Department of Neurosciences, 'Mondor Biomedical Research Institute', Paris-Est University, Faculty of Medicine, Créteil. 5. INSERM U1016, Genetics and development, Institut Cochin, Paris-Descartes University, CNRS UMR 8104, Genetics and development, Institut Cochin, Paris-Descartes University. 6. Department of Pediatric Neurology and Pediatric Neurophysiology, Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, AP-HP, Referral Center for Neuromuscular Diseases 'Garches-Necker-Mondor-Hendaye', Créteil. 7. Department of Dermatology, Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris. 8. Department of Pediatric Internal Medicine and Nephrology, Hôpital des Enfants, CHU de Toulouse, Toulouse. 9. Department of Pediatric Immunology-Hematology and Rheumatology, Paris-Descartes University, INSERM U 1163, Institut Imagine, AP-HP, Necker Hospital and. 10. Department of Immunology, CHU Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France. 11. Department of Pediatric Neurology and Pediatric Neurophysiology, Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, AP-HP, Referral Center for Neuromuscular Diseases 'Garches-Necker-Mondor-Hendaye', Créteil, INSERM U1016, Genetics and development, Institut Cochin, Paris-Descartes University, CNRS UMR 8104, Genetics and development, Institut Cochin, Paris-Descartes University.
Abstract
OBJECTIVE: Outcome of JDM is highly heterogeneous. Our objective was to determine clinical and muscle biopsy features associated with poor outcome and response to treatment. METHODS: Clinical data and muscle biopsy were obtained from a monocentric cohort of 29 patients. Clinical subgroups were defined by latent class model analysis of initial and follow-up parameters. Myopathological features were analysed using validated scores. Capillary loss was determined on reconstructions of transversal sections and assessed in the different age groups to take into account variations of muscle capillarization during post-natal development. Regression models were used to identify initial predictors of therapeutic response. RESULTS: Two distinct homogeneous subgroups of patients were identified according to clinical severity and pathological findings. The smallest group of patients (7/29) presented with severe JDM. Compared with the other group (22/29), patients had more severe muscle weakness at disease onset, low remission rate at 12 months, frequent subcutaneous limb oedema or gastrointestinal (GI) involvement and higher myopathological scores (capillary dropout, perifascicular necrosis/regeneration, fibres with internal myonuclei and fibrosis subscores). Relevance of capillary dropout to JDM severity was substantiated by age-based analysis, confirming its major role in JDM pathophysiology. Most of these manifestations could be related to vasculopathy (limb oedema, GI involvement, capillary dropout). Furthermore, Childhood Myositis Assessment Scale <34 with either GI involvement or muscle endomysial fibrosis at disease onset were the best predictors of poor response to treatment. CONCLUSION: Vasculopathy is prominent in severe JDM. Simple criteria can be used at initial evaluation to identify patients requiring a more intensive therapy.
OBJECTIVE: Outcome of JDM is highly heterogeneous. Our objective was to determine clinical and muscle biopsy features associated with poor outcome and response to treatment. METHODS: Clinical data and muscle biopsy were obtained from a monocentric cohort of 29 patients. Clinical subgroups were defined by latent class model analysis of initial and follow-up parameters. Myopathological features were analysed using validated scores. Capillary loss was determined on reconstructions of transversal sections and assessed in the different age groups to take into account variations of muscle capillarization during post-natal development. Regression models were used to identify initial predictors of therapeutic response. RESULTS: Two distinct homogeneous subgroups of patients were identified according to clinical severity and pathological findings. The smallest group of patients (7/29) presented with severe JDM. Compared with the other group (22/29), patients had more severe muscle weakness at disease onset, low remission rate at 12 months, frequent subcutaneous limb oedema or gastrointestinal (GI) involvement and higher myopathological scores (capillary dropout, perifascicular necrosis/regeneration, fibres with internal myonuclei and fibrosis subscores). Relevance of capillary dropout to JDM severity was substantiated by age-based analysis, confirming its major role in JDM pathophysiology. Most of these manifestations could be related to vasculopathy (limb oedema, GI involvement, capillary dropout). Furthermore, Childhood Myositis Assessment Scale <34 with either GI involvement or muscle endomysial fibrosis at disease onset were the best predictors of poor response to treatment. CONCLUSION:Vasculopathy is prominent in severe JDM. Simple criteria can be used at initial evaluation to identify patients requiring a more intensive therapy.
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