Table_1_Familial Periodic Fever, Aphthous Stomatitis, Pharyngitis and Adenitis Syndrome; Is It a Separate Disease?.docx

IntroductionPeriodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA) is the most common periodic fever syndrome in the pediatric population, yet its pathogenesis is unknown. PFAPA was believed to be sporadic but family clustering has been widely observed.
ObjectiveTo identify demographic and clinical differences between patients with PFAPA and a positive family history (FH+) as compared to those with no family history (FH−).
MethodsIn a database comprising demographic and clinical data of 273 pediatric PFAPA patients treated at two tertiary centers in Israel, 31 (14.3%) had FH+. Data from patients with FH+ were compared to data from those with FH−. Furthermore, family members (FMs) of those with FH+ were contacted via telephone for more demographic and clinical details.
ResultsThe FH+ group as compared to the FH− group had more myalgia (56 vs. 19%, respectively, p = 0.001), headaches (32 vs. 2%, respectively, p = 0.016), and a higher carrier frequency of M694V mutation (54% vs. 25%, respectively, p = 0.05). Colchicine was seen to be a more beneficial treatment for the FH+ group as compared to the FH− group; however, with no statistical significance (p = 0.096). FMs displayed almost identical characteristics to patients in the FH+ group except for greater arthralgia during flares (64 vs. 23%, respectively, p = 0.008), and compared to the FH− group they had more oral aphthae (68 vs. 43%, respectively, p = 0.002), myalgia/arthralgia (64 vs. 19%/16%, respectively, p < 0.0001), and higher rates of FH of Familial Mediterranean fever (FMF) (45 vs.15%, respectively, p = 0.003).
ConclusionsOur findings suggest that patients with a FH+ likely experience a different subset of disease with higher frequency of family history of FMF, arthralgia, myalgia, and might have a better response to colchicine compared to FH−. Colchicine prophylaxis for PFAPA should be considered in FH+.

## 引言
周期性发热、口疮性口炎、咽炎、淋巴结炎（Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis, PFAPA）是儿科人群中最常见的周期性发热综合征，但其发病机制尚未明确。既往认为PFAPA为散发性疾病，目前却已广泛观察到其家族聚集现象。

## 研究目的
明确存在阳性家族史（FH+）与阴性家族史（FH−）的PFAPA患者之间的人口学特征与临床差异。

## 研究方法
本研究纳入以色列两所三级医疗中心收治的273例儿科PFAPA患者的人口学与临床数据数据库，其中31例（14.3%）属于阳性家族史组（FH+）。将FH+组患者的数据与FH−组患者的数据进行对比分析；此外，通过电话联系FH+组患者的家庭成员（FMs），以获取更多人口学与临床细节信息。

## 研究结果
与FH−组相比，FH+组患者的肌痛发生率更高（56% vs. 19%，P=0.001）、头痛发生率更高（32% vs. 2%，P=0.016），且M694V突变携带率更高（54% vs. 25%，P=0.05）。秋水仙碱对FH+组的治疗获益似乎优于FH−组，但该差异无统计学显著性（P=0.096）。FH+组患者的家庭成员与FH+组患者表现出几乎一致的疾病特征，仅发作期关节痛发生率更高（64% vs. 23%，P=0.008）；与FH−组相比，该家庭成员群体出现更多口腔阿弗他溃疡（68% vs. 43%，P=0.002）、肌痛/关节痛（64% vs. 19%/16%，P<0.0001），且家族性地中海热（Familial Mediterranean Fever, FMF）家族史发生率更高（45% vs. 15%，P=0.003）。

## 研究结论
本研究结果提示，FH+型PFAPA患者可能属于疾病的不同亚型，其FMF家族史、关节痛、肌痛发生率更高，且相较于FH−型患者，秋水仙碱治疗应答可能更佳。因此，对于存在阳性家族史的PFAPA患者，应考虑采用秋水仙碱进行预防治疗。