Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy.
University of Trieste, Trieste, Italy.
Pediatr Rheumatol Online J. 2021 May 10;19(1):70. doi: 10.1186/s12969-021-00552-y.
Recurrent aphthous stomatitis with systemic signs of inflammation can be encountered in inflammatory bowel disease, Behçet's disease (BD), Systemic Lupus Erythematosus (SLE). In addition, it has been proposed that cases with very early onset in childhood can be underpinned by rare monogenic defects of immunity, which may require targeted treatments. Thus, subjects with early onset recurrent aphthous stomatitis receiving a clinical diagnosis of BD-like or SLE-like disease may deserve a further diagnostic workout, including immunologic and genetic investigations.
To investigate how an immunologic, genetic and transcriptomics assessment of interferon inflammation may improve diagnosis and care in children with recurrent aphthous stomatitis with systemic inflammation.
Subjects referred to the pediatric rheumatologist for recurrent aphthous stomatitis associated with signs of systemic inflammation from January 2015 to January 2020 were enrolled in the study and underwent analysis of peripheral lymphocyte subsets, sequencing of a 17-genes panel and measure of interferon score.
We enrolled 15 subjects (12 females, median age at disease onset 4 years). The clinical diagnosis was BD in 8, incomplete BD in 5, BD/SLE overlap in 1, SLE in 1. Pathogenic genetic variants were detected in 3 patients, respectively 2 STAT1 gain of function variants in two patients classified as BD/SLE overlap and SLE, and 1 TNFAIP3 mutation (A20 haploinsufficiency) in patients with BD. Moreover 2 likely pathogenic variants were identified in DNASE1L3 and PTPN22, both in patients with incomplete BD. Interferon score was high in the two patients with STAT1 GOF mutations, in the patient with TNFAIP3 mutation, and in 3 genetic-negative subjects. In two patients, the treatment was modified based on genetic results.
Although recurrent aphthous stomatitis associated with systemic inflammation may lead to a clinical diagnosis of BD or SLE, subjects with early disease onset in childhood deserve genetic investigation for rare monogenic disorders. A wider genetic panel may help disclosing the genetic background in the subset of children with increased interferon score, who tested negative in this study.
复发性阿弗他口腔溃疡伴全身炎症表现可发生于炎症性肠病、贝赫切特病（BD）、系统性红斑狼疮（SLE）。此外，有人提出，儿童期早期发病的病例可能与罕见的免疫单基因缺陷有关，这可能需要针对性治疗。因此，有早期复发性阿弗他口腔溃疡且临床诊断为 BD 样或 SLE 样疾病的患者可能需要进一步的诊断评估，包括免疫和遗传检查。
研究干扰素炎症的免疫、遗传和转录组学评估如何改善伴有全身炎症的复发性阿弗他口腔溃疡儿童的诊断和治疗。
本研究纳入了 2015 年 1 月至 2020 年 1 月因复发性阿弗他口腔溃疡伴全身炎症就诊于儿科风湿病医生的患者，并进行了外周血淋巴细胞亚群分析、17 基因panel 测序和干扰素评分检测。
共纳入 15 例患者（女 12 例，发病年龄中位数为 4 岁）。8 例临床诊断为 BD，5 例不完全 BD，1 例 BD/SLE 重叠，1 例 SLE。3 例患者检测到致病性基因突变，分别为 2 例 BD/SLE 重叠和 SLE 患者的 STAT1 功能获得性突变，1 例 BD 患者的 TNFAIP3 突变（A20 单倍体不足）。此外，在 2 例不完全 BD 患者中还发现了 2 个可能的致病性基因突变，分别位于 DNASE1L3 和 PTPN22 中。2 例 STAT1 GOF 突变患者、1 例 TNFAIP3 突变患者和 3 例基因阴性患者的干扰素评分较高。2 例患者根据基因结果调整了治疗方案。
虽然复发性阿弗他口腔溃疡伴全身炎症可能导致临床诊断为 BD 或 SLE，但儿童期早期发病的患者应进行遗传检查，以排除罕见的单基因疾病。更广泛的基因谱可能有助于揭示本研究中干扰素评分升高且基因检测阴性的儿童的遗传背景。
