Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Service de Médecine Interne 2, Maladies Auto-Imunes et Systémiques, Centre National de Référence des Histiocytoses, Hôpital Pitié-Salpêtrière, Paris, France.
Blood. 2020 Apr 16;135(16):1311-1318. doi: 10.1182/blood.2019002766.
Erdheim-Chester disease (ECD) is characterized by the infiltration of tissues by foamy CD68+CD1a- histiocytes, with 1500 known cases since 1930. Mutations activating the MAPK pathway are found in more than 80% of patients with ECD, mainly the BRAFV600E activating mutation in 57% to 70% of cases, followed by MAP2K1 in close to 20%. The discovery of BRAF mutations and of other MAP kinase pathway alterations, as well as the co-occurrence of ECD with LCH in 15% of patients with ECD, led to the 2016 revision of the classification of histiocytoses in which LCH and ECD belong to the "L" group. Both conditions are considered inflammatory myeloid neoplasms. Ten percent of ECD cases are associated with myeloproliferative neoplasms and/or myelodysplastic syndromes. Some of the most striking signs of ECD are the long bone involvement (80%-95%), as well as the hairy kidney appearance on computed tomography scan (63%), the coated aorta (40%), and the right atrium pseudo-tumoral infiltration (36%). Central nervous system involvement is a strong prognostic factor and independent predictor of death. Interferon-α seems to be the best initial treatment of ECD. Since 2012, more than 200 patients worldwide with multisystem or refractory ECD have benefitted from highly effective therapy with BRAF and MEK inhibitors. Targeted therapies have an overall, robust, and reproducible efficacy in ECD, with no acquired resistance to date, but their use may be best reserved for the most severe manifestations of the disease, as they may be associated with serious adverse effects and as-yet-unknown long-term consequences.
厄尔-当-切斯特病（ECD）的特征是组织中充满泡沫状 CD68+CD1a-组织细胞浸润，自 1930 年以来已发现 1500 例已知病例。超过 80%的 ECD 患者存在激活 MAPK 通路的突变，主要是 BRAFV600E 激活突变，占 57%至 70%，其次是 MAP2K1，接近 20%。BRAF 突变和其他 MAP 激酶通路改变的发现，以及 ECD 在 15%的 ECD 患者中与 LCH 共存，导致 2016 年对组织细胞增多症分类的修订，其中 LCH 和 ECD 属于“L”组。这两种情况都被认为是炎症性髓系肿瘤。10%的 ECD 病例与骨髓增生性肿瘤和/或骨髓增生异常综合征有关。ECD 最显著的特征之一是长骨受累（80%-95%），以及计算机断层扫描上的毛发状肾脏外观（63%）、覆盖的主动脉（40%）和右心房假性肿瘤浸润（36%）。中枢神经系统受累是一个强烈的预后因素和独立的死亡预测因素。干扰素-α似乎是 ECD 的最佳初始治疗方法。自 2012 年以来，全球 200 多名多系统或难治性 ECD 患者受益于 BRAF 和 MEK 抑制剂的高效治疗。靶向治疗在 ECD 中具有总体、强大和可重复的疗效，迄今为止尚未出现获得性耐药，但它们的使用可能最好保留用于疾病最严重的表现，因为它们可能与严重的不良反应和未知的长期后果有关。
