Background/Statement of PurposeSyndrome of Undifferentiated Recurrent Fevers (SURF) is characterized by recurrent fevers and autoinflammation without a confirmed molecular diagnosis of a Hereditary Recurrent Fever syndrome (HRF), and not fulfilling criteria for Periodic Fever, Adenitis, Pharyngitis, Aphthous stomatitis syndrome (PFAPA). The goal of this study was to characterize clinical features of SURF patients compared to PFAPA, and to analyze their cytokine signature, genetic variations, and responses to treatment.MethodsWe enrolled 46 patients followed at Cincinnati Children's Hospital Medical Center. Baseline data and inflammatory cytokines were collected at enrollment, and their clinical course was followed. Cytokine analysis was performed using a cytokine multiplex assay. Many patients had specific or whole exome genetic testing.ResultsThe prevalence of rash and arthralgias were higher in SURF compared to PFAPA. Pharyngitis and adenopathy were less frequent. A subset of SURF patients clustered together with elevated pro‐inflammatory cytokines and more frequently required biologic therapy. Focused analysis of WES data revealed that variants of unknown clinical significance (VUCS) were frequently identified in genes implicated in B cell development, immunodeficiencies, and inflammatory bowel disease risk. Treatments for SURF patients commonly included on‐demand steroids, colchicine, and anti‐IL1 therapy.ConclusionOur findings suggest SURF is a heterogeneous group but has distinct clinical and immunologic features from disorders like PFAPA. Patients have frequent VUCS, which may have relevance to disease pathogenesis. A subset of patients showed more inflammation and increased need for biologic use. Further research is necessary to define whether there exist distinct SURF endotypes and to better predict treatment outcomes.

中文翻译：

---

未分化复发性发热综合征 （SURF） 患者的临床、免疫学和遗传学特征


背景/目的陈述不分化复发性发热综合征 （SURF） 的特征是反复发热和自身炎症，没有确诊的遗传性复发性发热综合征 （HRF） 的分子诊断，也不符合周期性发热、腺炎、咽炎、口疮性口炎综合征 （PFAPA） 的标准。本研究的目的是表征 SURF 患者与 PFAPA 相比的临床特征，并分析他们的细胞因子特征、遗传变异和对治疗的反应。方法我们招募了 46 例在辛辛那提儿童医院医疗中心随访的患者。在入组时收集基线数据和炎性细胞因子，并跟踪他们的临床病程。使用细胞因子多重测定法进行细胞因子分析。许多患者进行了特异性或全外显子组基因检测。结果与 PFAPA 相比，SURF 中皮疹和关节痛的患病率更高。咽炎和淋巴结肿大较少见。一部分 SURF 患者聚集在一起，伴有促炎细胞因子升高，更频繁地需要生物治疗。对 WES 数据的重点分析显示，在与 B 细胞发育、免疫缺陷和炎症性肠病风险有关的基因中经常发现临床意义未知的变异 （VUCS）。SURF 患者的治疗通常包括按需类固醇、秋水仙碱和抗 IL1 疗法。结论我们的研究结果表明 SURF 是一个异质性群体，但与 PFAPA 等疾病具有不同的临床和免疫学特征。患者有频繁的 VUCS，这可能与疾病发病机制有关。一部分患者表现出更多的炎症和对生物制剂使用的需求增加。 需要进一步的研究来确定是否存在不同的 SURF 内型并更好地预测治疗结果。