Evans syndrome is a rare disease marked by a severe clinical course, high relapse rate, infectious and thrombotic complications, and sometimes fatal outcome. Management is highly heterogeneous. There are several case reports but few large retrospective studies and no prospective or randomised trials. Here, we report the results of the first consensus-based expert recommendations aimed at harmonising the diagnosis and management of Evans syndrome in adults. After reviewing the literature, we used a fuzzy Delphi consensus method, with two rounds of a 42-item questionnaire that were scored by a panel of 13 international experts from five countries using a 7-point Likert scale. Panellists were selected by the core panel on the basis of their personal experience and previous publications on Evans syndrome and immune cytopenias; they met virtually throughout 2023. The panellists recommended extensive clinical and laboratory diagnostic tests, including bone marrow evaluation and CT scan, and an aggressive front-line therapy with prednisone (with or without intravenous immunoglobulins), with different treatment durations and tapering for immune thrombocytopenia and autoimmune haemolytic anaemias (AIHAs). Rituximab was strongly recommended as first-line treatment in cold-type AIHA and as second-line treatment in warm-type AIHA and patients with immune thrombocytopenia and antiphospholipid antibodies, previous thrombotic events, or associated lymphoproliferative diseases. However, rituximab was discouraged for patients with immunodeficiency or severe infections, with the same applying to splenectomy. Thrombopoietin receptor agonists were recommended for chronic immune thrombocytopenia and in the case of previous grade 4 infection. Fostamatinib was recommended as third-line or further-line treatment and suggested as second-line therapy for patients with previous thrombotic events. Immunosuppressive agents have been moved to third-line or further-line treatment. The panellists recommended the use of recombinant erythropoietin in AIHA in the case of inadequate reticulocyte counts, use of the complement inhibitor sutimlimab for relapsed cold AIHA, and the combination of rituximab plus bendamustine in Evans syndrome secondary to lymphoproliferative disorders. Finally, recommendations were given for supportive therapy, platelet or red blood cell transfusions, and thrombotic and antibiotic prophylaxis. These consensus-based recommendations should facilitate best practice for diagnosis and management of Evans syndrome in clinical practice.

中文翻译：

---

成人 Evans 综合征的诊断和管理：首次共识推荐


埃文斯综合征是一种罕见疾病，其特点是临床病程严重、复发率高、感染和血栓形成并发症，有时甚至致命。治疗存在高度异质性。有几篇病例报告，但很少有大型回顾性研究，也没有前瞻性或随机试验。在这里，我们报告了旨在协调成人 Evans 综合征诊断和管理的首个基于共识的专家建议的结果。在回顾了文献后，我们使用了模糊德尔菲共识方法，由来自 5 个国家的 13 名国际专家组成的小组使用 7 分李克特量表对 42 项问卷进行了两轮评分。小组成员由核心小组根据他们的个人经验和以前关于 Evans 综合征和免疫性血细胞减少症的出版物选择;他们在整个 2023 年都以虚拟方式会面。小组成员推荐了广泛的临床和实验室诊断测试，包括骨髓评估和 CT 扫描，以及使用泼尼松龙（联合或不联合静脉注射免疫球蛋白）进行积极的一线治疗，免疫性血小板减少症和自身免疫性溶血性贫血 （AIHAs） 的治疗持续时间不同，逐渐减少。强烈建议将利妥昔单抗作为冷型 AIHA 的一线治疗，以及温型 AIHA 和免疫性血小板减少症和抗磷脂抗体患者、既往血栓形成事件或相关淋巴组织增生性疾病的二线治疗。然而，不鼓励免疫缺陷或严重感染患者使用利妥昔单抗，脾切除术也是如此。血小板生成素受体激动剂被推荐用于慢性免疫性血小板减少症和既往 4 级感染。 Fostamatinib 被推荐作为三线或远线治疗，并建议作为既往血栓形成事件患者的二线治疗。免疫抑制剂已移至三线或远线治疗。小组成员推荐在网织红细胞计数不足的情况下在 AIHA 中使用重组促红细胞生成素，使用补体抑制剂 sutimlimab 治疗复发性寒冷 AIHA，以及利妥昔单抗联合苯达莫司汀治疗继发于淋巴增生性疾病的 Evans 综合征。最后，对支持治疗、血小板或红细胞输注以及血栓形成和抗生素预防提出了建议。这些基于共识的建议应有助于在临床实践中诊断和管理 Evans 综合征的最佳实践。