Division of Hematology, AOU "Città della Salute e della Scienza di Torino", Torino, Italy.
Department of Molecular Biotechnologies and Health Sciences, University of Torino, Via Genova 3, 10126, Torino, Italy.
J Med Case Rep. 2021 Mar 7;15(1):105. doi: 10.1186/s13256-021-02726-4.
Human herpervirus-8/human immunodeficiency virus negative Idiopathic multicentric Castleman disease (iMCD) is a lymphoproliferative disorder sustained by a pro-inflammatory condition of hypercytokinemia mostly mediated by Interleukin-6 (IL-6). According to iMCD consensus guidelines, anti-IL-6 blockade should be the first-line therapy for iMCD. However, despite the existing therapeutic alternatives, a large proportion of iMCD patients still lacks an effective therapy.
Here, we report two real-life iMCD cases with a different response to IL-6 blockade. The first presented patient obtained a prompt resolution of symptoms and a complete regression of adenopathies after IL-6 blockade therapy administration. Conversely, the second patient did not respond neither to Rituximab and Etoposide association nor to IL-6 blockade therapy (both Siltuximab and Tocilizumab). Furthermore, Intravenous immunoglobulin, Cyclosporine A, Sirolimus and anti-Interleukin-1 Anakinra were all attempted without any results. Since no treatment was successful, after a further confirmation of iMCD diagnosis by a second lymph node biopsy, patient has been candidate for thalidomide, cyclophosphamide and prednisone association therapy.
The iMCD cases we reported are coherent with the evidences that IL-6 blockade is a safe and an effective therapy for iMCD. Despite this, more than half of patients do not respond to anti IL-6 drugs. In such cases, therapeutic alternatives could be represented by Sirolimus, targeting PI3K/AKT/mTOR signaling or by associations of conventional drugs such as thalidomide, cyclophosphamide and prednisone. However, the two reported iMCD cases, confirm the need to more deeply investigate iMCD pathogenesis and to better dissect the heterogeneity of the disease in order to develop novel, effective therapeutic strategies.
人类疱疹病毒 8/人类免疫缺陷病毒阴性特发性多中心 Castleman 病（iMCD）是一种由细胞因子过度分泌引起的炎症性疾病，主要由白细胞介素 6（IL-6）介导的淋巴组织增生性疾病。根据 iMCD 共识指南，抗 IL-6 阻断应作为 iMCD 的一线治疗方法。然而，尽管存在其他治疗选择，仍有很大一部分 iMCD 患者缺乏有效治疗方法。
在这里，我们报告了两例 iMCD 真实病例，它们对 IL-6 阻断的反应不同。第一个患者在接受 IL-6 阻断治疗后，症状迅速缓解，淋巴结肿大完全消退。相反，第二个患者对利妥昔单抗和依托泊苷联合治疗以及 IL-6 阻断治疗（西妥昔单抗和托珠单抗）均无反应。此外，静脉注射免疫球蛋白、环孢素 A、西罗莫司和白介素-1 拮抗剂 Anakinra 均无效。由于没有治疗成功，在第二次淋巴结活检进一步确认 iMCD 诊断后，患者成为沙利度胺、环磷酰胺和泼尼松联合治疗的候选者。
我们报告的 iMCD 病例与 IL-6 阻断是 iMCD 安全有效的治疗方法的证据一致。尽管如此，仍有一半以上的患者对抗 IL-6 药物无反应。在这种情况下，替代治疗方法可以是西罗莫司，靶向 PI3K/AKT/mTOR 信号通路，或传统药物的联合治疗，如沙利度胺、环磷酰胺和泼尼松。然而，这两个报道的 iMCD 病例证实，需要更深入地研究 iMCD 的发病机制，并更好地剖析疾病的异质性，以开发新的、有效的治疗策略。
