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免疫检查点抑制剂相关的结节病和类结节病反应的挑战:一个病例引发的叙述性综述

Challenges in sarcoidosis and sarcoid-like reactions associated to immune checkpoint inhibitors: A narrative review apropos of a case.

机构信息

Second Dermatology Department, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Department of Biomedical Sciences, School of Health Sciences, International Hellenic University, Alexandrian Campus, Thessaloniki, Greece.

出版信息

Dermatol Ther. 2021 Jan;34(1):e14618. doi: 10.1111/dth.14618. Epub 2020 Dec 10.

DOI:10.1111/dth.14618
PMID:33263945
Abstract

Sarcoidosis and sarcoid-like reactions (SLRs) may develop in association with various malignancies, as well as in association to certain oncologic drugs, including immune checkpoint inhibitors (ICIs). We aimed to perform a narrative review with regard to the development of ICIs-associated sarcoidosis or SLRs, and to discuss the corresponding diagnostic and therapeutic challenges raised in this scenario. Apropos of a melanoma patient developing SLRs while treated with ipilimumab and nivolumab, we searched for clinically evident, ICIs-associated sarcoidosis or SLRs in the English literature. We recorded the oncologic characteristics, including type of malignancy and type of ICI, the phenotypic characteristics of sarcoidosis/SLRs, as well as the impact on immunotherapy. Including our patient, we identified 80 ICIs-associated sarcoidosis or SLRs cases. Both sexes were equally affected (40 F/40 M) and the most common malignancy was melanoma (65/80, 81.3%). Concerning the oncologic treatment, there was a predilection for pembrolizumab (23/80, 28.7%), followed by the ipilimumab/nivolumab combination (21/80, 26.3%), ipilimumab (18/80, 22.5%), nivolumab (16/80, 20.0%). Although in the majority of the cases (52/80, 65.0%) there was no need for systemic prednisolone for the management of sarcoidosis, a significant proportion of patients finally discontinued ICIs treatment (44/80, 55.0%). Phenotypically, sarcoidosis and SLRs highly imitate oncologic progression posing diagnostic difficulties. A therapeutic dilemma is also raised when there is a need for systemic prednisolone, since the latter may jeopardize the therapeutic efficacy of immunotherapy. Sarcoidosis and SLRs, though rare, can present in oncologic patients treated with ICIs. Clinicians should be aware of this possibility and the related diagnostic and therapeutic challenges they have to face in this scenario.

摘要

结节病和结节样反应(SLR)可与各种恶性肿瘤相关,也可与某些肿瘤药物相关,包括免疫检查点抑制剂(ICI)。我们旨在对与 ICI 相关的结节病或 SLR 的发展进行叙述性综述,并讨论在此情况下提出的相应诊断和治疗挑战。在接受伊匹单抗和纳武单抗治疗的黑色素瘤患者出现 SLR 的情况下,我们在英文文献中搜索了临床明显的与 ICI 相关的结节病或 SLR。我们记录了肿瘤学特征,包括恶性肿瘤的类型和 ICI 的类型、结节病/SLR 的表型特征,以及对免疫治疗的影响。包括我们的患者在内,我们共确定了 80 例与 ICI 相关的结节病或 SLR 病例。男女发病率相等(40 例女性/40 例男性),最常见的恶性肿瘤是黑色素瘤(65/80,81.3%)。关于肿瘤治疗, pembrolizumab (23/80,28.7%)的应用更为常见,其次是伊匹单抗/纳武单抗联合治疗(21/80,26.3%)、伊匹单抗(18/80,22.5%)、纳武单抗(16/80,20.0%)。尽管在大多数情况下(52/80,65.0%),结节病的管理不需要全身泼尼松龙,但仍有相当一部分患者最终停止了 ICI 治疗(44/80,55.0%)。在表型上,结节病和 SLR 高度模仿肿瘤进展,导致诊断困难。当需要全身泼尼松龙治疗时,也会出现治疗上的困境,因为后者可能会危及免疫治疗的疗效。尽管结节病和 SLR 罕见,但在接受 ICI 治疗的肿瘤患者中可能会出现。临床医生应该意识到这种可能性,以及在这种情况下他们必须面对的相关诊断和治疗挑战。

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