title: Vasculopathy-related clinical and pathological features are associated with severe juvenile dermatomyositis.
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.
  
  
  CONCLUSIONS
  Vasculopathy is prominent in severe JDM. Simple criteria can be used at initial evaluation to identify patients requiring a more intensive therapy.
authors.affiliation: 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.
authors.forename: Cyril
authors.initials: C
authors.lastname: Gitiaux
authors.affiliation: 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.
authors.forename: Marie
authors.initials: M
authors.lastname: De Antonio
authors.affiliation: Department of Pathology, AP-HP, Albert Chenevier-Henri Mondor Hospital, Créteil.
authors.forename: Jessie
authors.initials: J
authors.lastname: Aouizerate
authors.affiliation: 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.
authors.forename: Romain K
authors.initials: RK
authors.lastname: Gherardi
authors.affiliation: INSERM U1016, Genetics and development, Institut Cochin, Paris-Descartes University, CNRS UMR 8104, Genetics and development, Institut Cochin, Paris-Descartes University.
authors.forename: Thomas
authors.initials: T
authors.lastname: Guilbert
authors.affiliation: 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.
authors.forename: Christine
authors.initials: C
authors.lastname: Barnerias
authors.affiliation: Department of Dermatology, Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris.
authors.forename: Christine
authors.initials: C
authors.lastname: Bodemer
authors.affiliation: Department of Pediatric Internal Medicine and Nephrology, Hôpital des Enfants, CHU de Toulouse, Toulouse.
authors.forename: Karine
authors.initials: K
authors.lastname: Brochard-Payet
authors.affiliation: Department of Pediatric Immunology-Hematology and Rheumatology, Paris-Descartes University, INSERM U 1163, Institut Imagine, AP-HP, Necker Hospital and.
authors.forename: Pierre
authors.initials: P
authors.lastname: Quartier
authors.affiliation: Department of Immunology, CHU Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Lucile
authors.initials: L
authors.lastname: Musset
authors.affiliation: INSERM U1016, Genetics and development, Institut Cochin, Paris-Descartes University, CNRS UMR 8104, Genetics and development, Institut Cochin, Paris-Descartes University.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Chazaud
authors.affiliation: 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.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Desguerre
authors.affiliation: Department of Pediatric Immunology-Hematology and Rheumatology, Paris-Descartes University, INSERM U 1163, Institut Imagine, AP-HP, Necker Hospital and.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bader-Meunier
mesh_terms: D000293:Adolescent; D001707:Biopsy, Needle; D002196:Capillaries / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003882:Dermatomyositis / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005602:France; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000473:pathology*; D011379:Prognosis; D012016:Reference Values; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D014652:Vascular Diseases / Q000150:complications / Q000473:pathology* / Q000503:physiopathology
keywords: juvenile dermatomyositis; muscle biopsy; outcome; prognostic factors; vasculopathy