咽扁桃体炎、口疮性口炎和淋巴结炎先于家族性地中海热二十年出现。

文献信息

中文摘要

背景： 家族性地中海热（FMF）与周期性发热、口疮性口炎、咽炎和颈部淋巴结炎（PFAPA）综合征共享先天免疫特征，但缺乏关于FMF被识别之前口咽部疾病负担的人群水平数据。
目的： 探讨后来被诊断为FMF的患者中类PFAPA口咽表型的程度、时间、特异性和治疗负担。
方法： 在以色列Leumit健康服务机构开展基于人群的匹配病例对照研究。接受秋水仙碱配药的FMF患者（n=3324）按出生年份和性别以1:4匹配至13296名对照。在诊断前长达20年和10年的窗口期内（30天黑障期），比较口咽部诊断、扁桃体/腺样体手术、抗生素配药和耳鼻喉科就诊情况，并使用链球菌、肥大和非耳鼻喉科阴性对照，采用错误发现率（FDR）校正。
结果： 2.6%的FMF患者记录了PFAPA诊断代码，而对照组为0.1%（比值比[OR] 25.4，95%置信区间14.3-48.5）。在诊断前长达20年，未来FMF患者有更多急性扁桃体炎（35.6% vs. 27.2%；OR 1.48，1.37-1.61）、病毒标记性扁桃体炎（OR 2.65）、口腔口疮（OR 1.72）和颈部淋巴结炎（OR 1.62；均q<0.05）；这些关联在诊断后持续存在。链球菌性咽痛编码未增加（终生OR 1.03，0.94-1.14）。抗生素配药和耳鼻喉科就诊增加；单纯扁桃体切除术更频繁（OR 2.51），但手术比较未通过FDR校正。
结论： FMF与一种非链球菌性、类PFAPA的口咽表型相关，该表型可在诊断前多年被检出。反复发作的咽扁桃体炎伴口疮或颈部淋巴结炎，且未证实链球菌性疾病，可能是高危人群中考虑FMF的临床线索。

英文摘要

BACKGROUND: Familial Mediterranean fever (FMF) and periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome share innate-immune features, but population-level data on oropharyngeal morbidity before FMF recognition are lacking.
OBJECTIVES: To examine the magnitude, timing, specificity, and treatment burden of a PFAPA-like oropharyngeal phenotype in patients later diagnosed with FMF.
METHODS: Population-based matched case-control study in Leumit Health Services, Israel. FMF patients with colchicine dispensing (n = 3324) were matched 1:4 by birth year and sex to 13,296 controls. Oropharyngeal diagnoses, tonsil/adenoid surgery, antibiotic dispensing, and ear, nose, and throat (ENT) visits were compared across windows up to 20 and 10 years before diagnosis (30-day blackout), using streptococcal, hypertrophy, and non-ENT negative controls with false discovery rate (FDR) adjustment.
RESULTS: A PFAPA diagnostic code was recorded in 2.6% of FMF patients versus 0.1% of controls (odds ratio [OR] 25.4, 95% confidence interval 14.3-48.5). Up to 20 years before diagnosis, future FMF patients had more acute tonsillitis (35.6% vs. 27.2%; OR 1.48, 1.37-1.61), viral-labeled tonsillitis (OR 2.65), oral aphthae (OR 1.72), and cervical lymphadenitis (OR 1.62; all q < 0.05); associations persisted after diagnosis. Streptococcal sore-throat coding was not increased (lifelong OR 1.03, 0.94-1.14). Antibiotic dispensing and ENT visits were increased; tonsillectomy alone was more frequent (OR 2.51), although surgical comparisons did not survive FDR correction.
CONCLUSIONS: FMF is associated with a non-streptococcal, PFAPA-like oropharyngeal phenotype detectable years before diagnosis. Recurrent pharyngotonsillitis with aphthae or cervical adenitis, without demonstrated streptococcal disease, may be a clinical cue to consider FMF in at-risk populations.