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,
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.
Rheumatology (Oxford). 2016 Mar;55(3):470-9. doi: 10.1093/rheumatology/kev359. Epub 2015 Sep 30.
Outcome of JDM is highly heterogeneous. Our objective was to determine clinical and muscle biopsy features associated with poor outcome and response to treatment.
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.
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.
Vasculopathy is prominent in severe JDM. Simple criteria can be used at initial evaluation to identify patients requiring a more intensive therapy.
皮肌炎（JDM）的预后差异很大。本研究旨在确定与不良预后和治疗反应相关的临床和肌肉活检特征。
从单中心队列中获取 29 例患者的临床数据和肌肉活检。采用潜在类别模型分析初始和随访参数，对临床亚组进行定义。使用验证后的评分分析肌肉病理特征。在不同年龄组的横切面重建中确定毛细血管丢失，并评估其变化，以考虑到出生后发育过程中肌肉毛细血管化的变化。使用回归模型确定治疗反应的初始预测因子。
根据临床严重程度和病理发现，确定了两个具有明显同质性的患者亚组。最小的一组患者（7/29）表现为严重的 JDM。与另一组患者（22/29）相比，这些患者在疾病发作时肌肉无力更严重，12 个月时缓解率低，常出现四肢皮下水肿或胃肠道（GI）受累，且肌病理评分更高（毛细血管缺失、束周坏死/再生、纤维内有核和纤维化亚评分）。基于年龄的分析证实了毛细血管缺失与 JDM 严重程度的相关性，进一步证实了其在 JDM 发病机制中的主要作用。这些表现大多与血管病变有关（四肢水肿、GI 受累、毛细血管缺失）。此外，发病时存在肌炎评估量表（Childhood Myositis Assessment Scale，CMAS）<34 分且有 GI 受累或肌肉内肌膜纤维化是治疗反应不佳的最佳预测因子。
血管病变在严重的 JDM 中很突出。在初始评估时，可以使用简单的标准来识别需要更强化治疗的患者。
