阿卡替尼诱导的多发性口腔溃疡：一例病例报告及文献综述

文献信息

中文摘要

阿卡替尼是一种布鲁顿酪氨酸激酶抑制剂，是治疗血液系统恶性肿瘤的有效疗法。尽管通常耐受性良好，但它可能引起不良事件，包括罕见的口腔毒性。一名有13年慢性淋巴细胞白血病病史的94岁女性因严重口腔疼痛和吞咽困难就诊。既往曾使用多种药物，包括伊布替尼，最近使用的是阿卡替尼（100 mg，每日两次），在出现血尿和疼痛性口腔溃疡后停药。检查发现硬腭、舌背和颊黏膜存在深溃疡。血液学评估显示白细胞增多（WBC 63 × 10⁹/L），无中性粒细胞减少/血小板减少。定制局部漱口水在2周内使口腔病变接近完全消退。7个月后重新引入阿卡替尼，引起较轻的口腔溃疡，经相同方案治疗后消退，且未停用阿卡替尼。因果关系由时间关联、停药后消退以及再暴露后复发所支持。本病例报告了阿卡替尼相关脱靶激酶效应损害黏膜愈合。

英文摘要

Acalabrutinib, a Bruton's tyrosine kinase inhibitor, is an effective therapy for hematologic malignancies. Although generally well-tolerated, it may cause adverse events including rare oral toxicities. A 94-year-old woman with a 13-year history of chronic lymphocytic leukemia presented with severe oral pain and dysphagia. Previously, multiple agents had been administered, including ibrutinib, and most recently acalabrutinib (100 mg two times per day), which was discontinued following the onset of hematuria and painful oral ulcerations. Examination revealed deep ulcerations affecting the hard palate, dorsum of tongue, and buccal mucosa. Hematologic evaluation showed leukocytosis (WBC 63 × 10⁹/L) without neutropenia/thrombocytopenia. A customized topical mouthwash achieved near-complete resolution of oral lesions within 2 weeks. Reintroduction of acalabrutinib, 7 months later, caused milder oral ulcerations which resolved with the same regimen without discontinuation of acalabrutinib. Causality was supported by the temporal association, resolution upon withdrawal, and recurrence on rechallenge. This case reports acalabrutinib-associated off-target kinase effects impairing mucosal healing.