替泽利尤单抗治疗期间持续性疑似变应性真菌性鼻窦炎经修正手术后改善：一例病例报告

文献信息

中文摘要

变应性真菌性鼻窦炎（AFRS）是伴鼻息肉的2型慢性鼻窦炎（CRSwNP）中一个临床独特的亚型，其特征为总IgE显著升高、真菌致敏以及伴有骨重塑的膨胀性疾病。确诊需要满足Bent和Kuhn的全部五项标准，包括组织病理学显示嗜酸性黏蛋白而无组织侵袭以及真菌染色阳性。替泽利尤单抗是一种针对胸腺基质淋巴细胞生成素（抗TSLP）的单克隆抗体，在重度CRSwNP中已有3期证据，但尚未在AFRS中专门评估。我们报告一例32岁女性，具有AFRS样CRSwNP表型，临床和影像学怀疑但未获组织学确诊（血清总IgE 1,330 IU/mL；对曲霉、链格孢、青霉和念珠菌多种真菌致敏），并患有重度哮喘。在因重度哮喘而非因鼻窦疾病启用替泽利尤单抗治疗的11个月期间，鼻窦疾病未得到控制：22项鼻窦结局测试（SNOT-22）评分仍为重度（85→89/110），影像学显示上颌窦病变间期进展，左侧后组筛窦黏液囊肿持续存在并压迫视神经管和眼眶，该囊肿在生物制剂治疗前影像中即已存在。需要修正性内镜鼻窦手术（FESS）；术后两个月SNOT-22显著改善至48/110，哮喘控制部分改善（哮喘控制测试[ACT] 8→15/25）。时间模式与手术后改善而非抗TSLP治疗改善相符，尽管围手术期糖皮质激素、继续药物治疗、依从性变化和疾病自然病程也可能有所贡献。仅有两月术后随访的单一非对照观察不能确定TSLP阻断对AFRS无效；它确实说明固定结构性病变可能无法仅通过生物制剂治疗解决。需要对组织学确诊的AFRS进行抗TSLP治疗的前瞻性专门研究。

英文摘要

Allergic fungal rhinosinusitis (AFRS) is a clinically distinct subset of type 2 chronic rhinosinusitis with nasal polyps (CRSwNP), characterized by markedly elevated total IgE, fungal sensitization, and expansile disease with bony remodeling. Definitive diagnosis requires all five Bent and Kuhn criteria, including histopathological demonstration of eosinophilic mucin without tissue invasion and a positive fungal stain. Tezepelumab, a monoclonal antibody against thymic stromal lymphopoietin (anti-TSLP), has phase 3 evidence in severe CRSwNP but has not been evaluated specifically in AFRS. We report a 32-year-old woman with an AFRS-like CRSwNP phenotype, clinically and radiologically suspected but not histologically confirmed (total serum IgE 1,330 IU/mL; fungal polysensitization to Aspergillus, Alternaria, Penicillium and Candida) and severe asthma. During 11 months of tezepelumab prescribed for severe asthma rather than initiated for sinonasal disease, sinonasal disease was not controlled: the 22-item Sino-Nasal Outcome Test (SNOT-22) score remained severe (85→89/110) and imaging showed interval progression of maxillary disease, with persistence of a left posterior ethmoidal mucocele encroaching on the optic canal and orbit that had already been present on pre-biologic imaging. Revision endoscopic sinus surgery (FESS) was required; two months postoperatively the SNOT-22 improved markedly to 48/110 and asthma control improved partially (Asthma Control Test [ACT] 8→15/25). The temporal pattern is compatible with improvement following surgery rather than anti-TSLP therapy, although perioperative corticosteroids, continued medical treatment, changes in adherence and the natural course of disease may also have contributed. A single, uncontrolled observation with only two months of postoperative follow-up cannot establish that TSLP blockade is ineffective in AFRS; it does illustrate that fixed structural disease may not be addressed by biologic therapy alone. Dedicated prospective studies of anti-TSLP therapy in histologically confirmed AFRS are needed.