Miyamae Takako, Hanaya Aki, Kawamoto Manabu, Tani Yumi, Kawaguchi Yasushi, Yamanaka Hisashi
Department of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan.
From the Institute of Rheumatology.
J Clin Rheumatol. 2020 Mar;26(2):60-62. doi: 10.1097/RHU.0000000000000929.
This is a noncomparative study performed to determine if fever pattern is related to a diagnosis of autoinflammatory disease (AID) in pediatric- and adult-onset patients.
The final diagnosis of patients suspected to have AID was evaluated against gene polymorphisms known to be responsible for AID, clinical manifestations, and fever pattern, in our institute from 2005 to 2016. Genomic DNA was isolated from patients' peripheral blood, and polymerase chain reaction was used to amplify the indicated exons of 12 genes: MEFV, TNFRSF1A, MVK, NLRP3, NOD2, LI1RN, IL36RN, PSMB8, NALP12, PSTPIP1, TNFAIP3, and NLRC4. Genetic polymorphisms of the above genes were examined.
All 210 individuals (135 pediatric onset and 75 adult onset) were classified into the following 3 subgroups: (1) periodic fever (n = 74 and 25 for pediatric and adult onset, respectively), (2) recurrent fever lacking a regular period (n = 47 and 41), and (3) persistent fever (n = 14 and 9). Diagnosis of AID was highest in subgroup 1 (70.2% and 36.0% for pediatric and adult onset, respectively), followed by subgroup 2(29.8% and 17.1%), including PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and adenitis) (n = 34 and 1), familial Mediterranean fever (n = 22 and 13), cryopyrin-associated periodic syndrome (n = 6 and 1), and tumor necrosis factor receptor-associated periodic syndrome (n = 3 and 1 for pediatric and adult onset, respectively). None were diagnosed with AID in subgroup 3.
Autoinflammatory disease was more likely to be diagnosed in pediatric-onset patients compared with adult-onset patients. In both age-onset groups, AID was primarily identified in patients with periodic fever and never diagnosed in patients with persistent fever. Our findings indicate that fever pattern is a useful factor to estimate the probability of AID.
本研究为非对照研究，旨在确定发热模式是否与儿童及成人发病的自身炎症性疾病（AID）诊断相关。
2005年至2016年期间，在我们研究所，针对疑似患有AID的患者，根据已知与AID相关的基因多态性、临床表现和发热模式进行最终诊断评估。从患者外周血中分离基因组DNA，并使用聚合酶链反应扩增12个基因的指定外显子：MEFV、TNFRSF1A、MVK、NLRP3、NOD2、LI1RN、IL36RN、PSMB8、NALP12、PSTPIP1、TNFAIP3和NLRC4。检测上述基因的遗传多态性。
所有210名个体（135名儿童发病和75名成人发病）被分为以下3个亚组：（1）周期性发热（儿童发病和成人发病分别为74例和25例），（2）无规律周期的反复发热（47例和41例），（3）持续性发热（14例和9例）。AID诊断在亚组1中最高（儿童发病和成人发病分别为70.2%和36.0%），其次是亚组2（29.8%和(17.1%)），包括PFAPA（周期性发热、阿弗他口炎、咽炎和腺炎）（34例和1例）、家族性地中海热（22例和13例）、冷吡啉相关周期性综合征（6例和1例）以及肿瘤坏死因子受体相关周期性综合征（儿童发病和成人发病分别为3例和1例）。亚组3中无人被诊断为AID。
与成人发病患者相比，儿童发病患者更有可能被诊断为自身炎症性疾病。在两个发病年龄组中，AID主要在周期性发热患者中被识别，而在持续性发热患者中从未被诊断。我们的研究结果表明，发热模式是估计AID可能性的一个有用因素。
