肿瘤免疫治疗致免疫性输尿管炎及膀胱炎1例的诊治报告与分析

Immune-related ureteritis and cystitis induced by immune checkpoint inhibitor therapy: a case report and literature review

摘要

目的 免疫检查点抑制剂（ICIs）引发的免疫相关不良反应（irAEs）日益受到关注。泌尿系统irAEs少见，同时累及输尿管和膀胱的irAEs病例罕有报道。本文报告1例以为泌尿系irAEs的识别与诊治提供参考。方法 报道1例患者详细诊治经过并结合文献分析其临床特点。结果 该54岁肺腺癌患者接受信迪利单抗治疗4个疗程后，出现尿频、尿急、尿痛及腰痛，膀胱镜下呈“类间质性膀胱炎”表现，经排除感染和肿瘤因素后诊断为免疫性输尿管炎/膀胱炎（CTCAE 3级）。给予糖皮质激素[甲泼尼龙0.8 mg/（kg/d）起始，逐渐减量]联合吗替麦考酚酯（1.5 g/d）治疗。治疗中发现膀胱炎迅速缓解且未复发，而输尿管炎在激素减量时反复复发两次，提示两部位存在不同的激素敏感性。经调整减量速度（≤2 mg/周）并延长免疫抑制剂疗程后，患者完全缓解。结论 本病例首次报道信迪利单抗相关泌尿系统irAE、详细记录膀胱与输尿管的不同治疗反应，初次探索了应用吗替麦考酚酯联合治疗。临床启示：①膀胱症状缓解不代表全尿路炎症控制，需持续监测输尿管；②输尿管受累时需更谨慎的激素减量策略；③吗替麦考酚酯在泌尿系统irAE中安全有效；④免疫性膀胱炎镜下可呈“类间质性膀胱炎”表现，在无活检条件下，其对免疫抑制治疗的迅速应答可作为反证诊断的重要依据。

Abstract

Objective Immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) have garnered increasing attention. Urologic irAEs are uncommon, and cases involving both the ureter and bladder are particularly rare. This article reports such a case to provide insights into the recognition and management of urologic irAEs. Methods The detailed diagnosis and treatment of a case were reported and its clinical characteristics were analyzed in the context of the relevant literature. Results The 54-year-old patient with lung adenocarcinoma developed increased urinary frequency, urgency, dysuria, and lower back pain after four cycles of Sintilimab treatment. Cystoscopy revealed an “interstitial cystitis-like” appearance. After infectious and neoplastic etiologies were excluded, the patient was diagnosed with immune-related ureteritis/cystitis (CTCAE grade 3). The patient was treated with systemic corticosteroids [methylprednisolone 0.8 mg/(kg/d), tapered gradually] combined with mycophenolate mofetil (1.5 g/d). Notably, cystitis resolved rapidly without recurrence, while ureteritis recurred twice during steroid tapering, suggesting differential steroid sensitivity between the two sites. After the tapering rate (≤2 mg/week) was adjusted and immunosuppressant therapy was prolonged, complete remission was achieved. Conclusion This is the first reported case of Sintilimab-related urinary irAEs, the first to detail differential treatment responses between bladder and ureters, and the first to employ mycophenolate mofetil in this context. The findings indicate that resolution of bladder symptoms does not indicate complete urinary tract inflammation control, more cautious steroid tapering is needed when ureters are involved, mycophenolate mofetil is safe and effective for urinary irAEs, and immune-related cystitis can present with an “interstitial cystitis-like” appearance under cystoscopy. In the absence of a biopsy, its rapid response to immunosuppressive therapy can serve as an important basis for retrospective diagnosis.

关键词

免疫检查点抑制剂 / 免疫相关不良反应 / 输尿管炎 / 膀胱炎 / 信迪利单抗

Key words

immune checkpoint inhibitors / immune-related adverse events / ureteritis / cystitis / Sintilimab

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