Rapid and sustained control of itch and reduction in Th2 bias by dupilumab in a patient with Sezary syndrome
Rapid and sustained control of itch and reduction in Th2 bias by dupilumab in a patient with Sezary syndrome
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DOI：
10.1111/jdv.17001
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发表时间：
2020-11-22
影响因子：
9.2
通讯作者：
Schlapbach, C.
中科院分区：
文献类型：
--
作者：
Steck, O.;Bertschi, N. L.;Schlapbach, C.
背景：Sezary综合征是皮肤T细胞淋巴瘤的白血病变异型，预后差。除了干细胞移植外，目前对SS的治疗尚不能治愈。相反，它们旨在减少疾病负担和提高生活质量。然而，瘙痒症-这些患者生活质量受损的主要原因-是众所周知的难以治疗。目的探讨dupilumab联合2型细胞因子阻断治疗Sezary综合征的临床和免疫学效果继续进行体外循环血液置换术对患者的血液和皮肤样本进行了44周的密切临床和免疫学监测。与患者的淋巴瘤细胞进行体外试验，以解决Sezary细胞对Th 2 cytokines.Results的反应dupilumab的影响，临床上，dupilumab治疗诱导快速和持续减少瘙痒和改善皮肤和淋巴结的参与。在血液和皮肤中，观察到Th 2偏倚的降低。有趣的是，血液中的淋巴细胞计数和Sezary细胞增加，随后在dupilumab治疗下稳定。在体外，dupilumab废除了抗凋亡和激活效应的Th 2细胞因子对Sezary cells.Conclusions在这Sezary患者，抑制IL-4和IL-13信号转导与显着的临床效益方面的生活质量，瘙痒和局部皮质类固醇的使用。虽然安全性仍然是一个重要的问题，我们的数据支持未来的探索Th 2调节支持性治疗塞扎里综合征。
Background Sezary syndrome is a leukaemic variant of cutaneous T-cell lymphoma with poor prognosis. With the exception of stem cell transplantation, current treatments for SS are not curative. Rather, they aim at reducing disease burden and improving quality of life. Yet, pruritus - the major cause for impaired quality of life in these patients - is notoriously difficult to treat. Thus, supportive treatments addressing agonizing pruritus are urgently needed.Objectives To explore the clinical and immunological effects of type 2 cytokine blockade with dupilumab as supportive treatment in Sezary syndrome.Methods A Sezary syndrome patient with stable disease but intractable pruritus was treated with dupilumab in combination with continued extracorporeal photopheresis. Close clinical and immunological monitoring on blood and skin samples from the patient was performed over 44 weeks. In vitro assays with patient's lymphoma cells were performed to address effects of dupilumab on Sezary cell's response to Th2 cytokines.Results Clinically, dupilumab treatment induced rapid and sustained reduction in itch and improvement of skin and lymph node involvement. In both blood and skin, a reduction in Th2 bias was observed. Intriguingly, lymphocyte counts and Sezary cells in blood increased and later stabilized under dupilumab treatment. In vitro, dupilumab abrogated the anti-apoptotic and activating effects of Th2 cytokines on Sezary cells.Conclusions In this Sezary patient, inhibition of IL-4 and IL-13 signalling was associated with striking clinical benefit in terms of quality of life, pruritus and use of topical corticosteroids. While safety remains an important concern, our data support the future exploration of Th2 modulation for supportive care in Sezary Syndrome.