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胃巨细胞病毒感染,在黑色素瘤患者使用依匹单抗和纳武单抗联合治疗中为罕见不良反应。

Cytomegalovirus gastritis as a rare adverse event during combined ipilimumab and nivolumab in a patient with melanoma.

机构信息

Medical Oncology Unit, Department of Oncology, ASST Sette Laghi, Ospedale di Circolo e Fondazione Macchi.

Pathology Unit, ASST Sette Laghi, Ospedale di Circolo e Fondazione Macchi.

出版信息

Melanoma Res. 2024 Aug 1;34(4):386-389. doi: 10.1097/CMR.0000000000000981. Epub 2024 May 20.

DOI:10.1097/CMR.0000000000000981
PMID:38768445
Abstract

Immunotherapy has improved survival outcomes of patients with advanced melanoma. Lower gastrointestinal tract immune-related adverse events (irAEs) are common during treatment; however, gastritis is not frequently observed. Herein, we report a case of severe cytomegalovirus (CMV)-related gastritis in a patient treated with ipilimumab and nivolumab for metastatic melanoma. This report presents a 60-year-old woman with stage IV BRAF wild-type melanoma. After the second course of ipilimumab-nivolumab, the patient reported epigastric discomfort after meals, anorexia, and subsequent nausea, vomiting, epigastric pain, and weight loss. Disease staging with PET/CT scan showed very good partial response and diffuse gastroduodenitis. The patient underwent esophagogastroduodenoscopy, showing severe esophageal candidiasis and diffuse hemorrhagic, edematous, and ulcerative mucosa in the whole gastric wall. Biopsies of the gastric wall were obtained. Before receipt of the final pathology report, the patient was empirically started on corticosteroids based on the clinical suspicion of immune-related gastritis, without improvement of symptoms. The hematoxylin-eosin staining demonstrated active gastritis with diffuse nuclear cytopathic viral inclusions in epithelial and interstitial cells; CMV infection was confirmed with immunohistochemical staining. The patient started ganciclovir and fluconazole, with rapid improvement of symptoms. This case presents a rare instance of CMV gastritis in a patient receiving combined anti-PD1 and anti-CTLA4 , in the absence of immune-suppression to manage an irAE. In the case of suggestive symptoms of irAEs, a high index of clinical suspicion is required to rule out concomitant or isolated infective disease. Guidelines for prophylaxis and treatment of these patients are needed, to optimize treatment results.

摘要

免疫疗法改善了晚期黑色素瘤患者的生存结果。在治疗过程中,下消化道免疫相关不良事件(irAE)很常见;然而,胃炎并不常见。在此,我们报告了一例接受 ipilimumab 和 nivolumab 治疗转移性黑色素瘤的患者发生严重巨细胞病毒(CMV)相关性胃炎。本报告介绍了一位 60 岁女性,患有 IV 期 BRAF 野生型黑色素瘤。在接受 ipilimumab-nivolumab 第二疗程后,患者在餐后出现上腹部不适、食欲不振,随后出现恶心、呕吐、上腹痛和体重减轻。PET/CT 扫描显示疾病分期为很好的部分缓解和弥漫性胃十二指肠炎。患者接受了食管胃十二指肠镜检查,显示严重的食管念珠菌病和弥漫性出血、水肿和溃疡的整个胃壁黏膜。进行了胃壁活检。在收到最终病理报告之前,根据免疫相关胃炎的临床怀疑,对患者进行了经验性皮质类固醇治疗,但症状没有改善。苏木精-伊红染色显示活动性胃炎,上皮细胞和间质细胞中弥漫性核细胞病变包涵体;免疫组织化学染色证实了 CMV 感染。患者开始使用更昔洛韦和氟康唑治疗,症状迅速改善。该病例为一例罕见的在接受联合抗 PD1 和抗 CTLA4 治疗的患者中发生的 CMV 胃炎,而无免疫抑制治疗 irAE。在出现 irAE 提示症状的情况下,需要高度的临床怀疑指数来排除伴随或孤立的传染病。需要为这些患者制定预防和治疗指南,以优化治疗结果。

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