Aladjidi Nathalie, Fernandes Helder, Leblanc Thierry, Vareliette Amélie, Rieux-Laucat Frédéric, Bertrand Yves, Chambost Hervé, Pasquet Marlène, Mazingue Françoise, Guitton Corinne, Pellier Isabelle, Roqueplan-Bellmann Françoise, Armari-Alla Corinne, Thomas Caroline, Marie-Cardine Aude, Lejars Odile, Fouyssac Fanny, Bayart Sophie, Lutz Patrick, Piguet Christophe, Jeziorski Eric, Rohrlich Pierre, Lemoine Philippe, Bodet Damien, Paillard Catherine, Couillault Gérard, Millot Frédéric, Fischer Alain, Pérel Yves, Leverger Guy
Department of Pediatric Hematology, University Hospital of Bordeaux , Bordeaux , France ; Centre de Référence National des Cytopénies Autoimmunes de l'Enfant (CEREVANCE), University Hospital of Bordeaux , Bordeaux , France ; CIC 0005, INSERM CICP, University Hospital of Bordeaux , Bordeaux , France.
Centre de Référence National des Cytopénies Autoimmunes de l'Enfant (CEREVANCE), University Hospital of Bordeaux , Bordeaux , France ; CIC 0005, INSERM CICP, University Hospital of Bordeaux , Bordeaux , France.
Front Pediatr. 2015 Sep 29;3:79. doi: 10.3389/fped.2015.00079. eCollection 2015.
Evans syndrome (ES) is a rare autoimmune disorder whose long-term outcome is not well known. In France, a collaborative pediatric network set up via the National Rare Disease Plan now provides comprehensive clinical data in children with this disease. Patients aged less than 18 years at the initial presentation of autoimmune cytopenia have been prospectively included into a national observational cohort since 2004. The definition of ES was restricted to the simultaneous or sequential association of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP). Cases were deemed secondary if associated with a primitive immunodeficiency or systemic lupus erythematosus. In December 2014, we analyzed the data pertaining to 156 children from 26 centers with ES whose diagnosis was made between 1981 and 2014. Median age (range) at the onset of cytopenia was 5.4 years (0.2-17.2). In 85 sequential cases, the time lapse between the first episodes of AIHA and ITP was 2.4 years (0.1-16.3). The follow-up period as from ES diagnosis was 6.5 years (0.1-28.8). ES was secondary, revealing another underlying disease, in 10% of cases; various associated immune manifestations (mainly lymphoproliferation, other autoimmune diseases, and hypogammaglobulinemia) were observed in 60% of cases; and ES remained primary in 30% of cases. Five-year ITP and AIHA relapse-free survival were 25 and 61%, respectively. Overall, 69% of children required one or more second-line immune treatments, and 15 patients (10%) died at the age of 14.3 years (1.7-28.1). To our knowledge, this is the first consistent long-term clinical description of this rare syndrome. It underscores the high rate of associated immune manifestations and the burden of long-term complications and treatment toxicity. Future challenges include (1) the identification of the underlying genetic defects inducing immune dysregulation and (2) the need to better characterize patient subgroups and second-line treatment strategies.
伊文氏综合征（ES）是一种罕见的自身免疫性疾病，其长期预后尚不清楚。在法国，通过国家罕见病计划建立的一个协作性儿科网络现在提供了患有这种疾病儿童的全面临床数据。自2004年以来，首次出现自身免疫性血细胞减少症时年龄小于18岁的患者被前瞻性纳入一个全国性观察队列。ES的定义仅限于自身免疫性溶血性贫血（AIHA）和免疫性血小板减少性紫癜（ITP）同时或相继出现。如果与原发性免疫缺陷或系统性红斑狼疮相关，则病例被视为继发性。2014年12月，我们分析了来自26个中心的156例ES患儿的数据，这些患儿的诊断时间在1981年至2014年之间。血细胞减少症发作时的中位年龄（范围）为5.4岁（0.2 - 17.2岁）。在85例相继出现的病例中，AIHA和ITP首次发作之间的时间间隔为2.4年（0.1 - 16.3年）。自ES诊断后的随访期为6.5年（0.1 - 28.8年）。10%的病例中ES是继发性的，揭示了另一种潜在疾病；60%的病例观察到各种相关的免疫表现（主要是淋巴细胞增殖、其他自身免疫性疾病和低丙种球蛋白血症）；30%的病例中ES仍为原发性。5年无ITP和AIHA复发生存率分别为25%和61%。总体而言，69%的儿童需要一种或多种二线免疫治疗，15例患者（10%）在14.3岁（1.7 - 28.1岁）时死亡。据我们所知，这是对这种罕见综合征的首次连贯的长期临床描述。它强调了相关免疫表现的高发生率以及长期并发症和治疗毒性的负担。未来的挑战包括：（1）识别导致免疫失调的潜在基因缺陷；（2）需要更好地对患者亚组和二线治疗策略进行特征描述。
