Department of Pediatrics, Division of Allergy, Immunology and Rheumatology, University of California-San Diego, La Jolla, CA, United States of America.
Rady Children's Foundation, Rady Children's Hospital, San Diego, CA, United States of America; Department of Surgery, Division of Otolaryngology, University of California San Diego, La Jolla, CA, United States of America.
Clin Immunol. 2021 May;226:108697. doi: 10.1016/j.clim.2021.108697. Epub 2021 Feb 24.
Autoinflammatory disorders of the innate immune system present with recurrent episodes of inflammation often beginning in early childhood. While there are now more than 30 genetically-defined hereditary fever disorders, many patients lack a clear diagnosis. Many pediatric patients are often grouped with patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome despite failing to meet diagnostic criteria. Here, we categorize these patients as syndrome of undifferentiated recurrent fever (SURF), and identify the unique features which distinguish them from the PFAPA syndrome. SURF patients were more likely to report gastrointestinal symptoms of nausea, vomiting and abdominal pain, and experienced inconsistent responses to on-demand steroid therapy compared to PFAPA patients. For this previously undefined cohort, an optimal course of therapy remains uncertain, with medical and surgical therapies largely driven by parental preference. A subset of patients with SURF underwent tonsillectomy with complete resolution. Flow cytometric evaluation demonstrates leukocytic populations distinct from PFAPA patients, with reduced CD3+ T cell numbers. SURF patient tonsils were predominantly characterized by an IL-1 signature compared to PFAPA, even during the afebrile period. Peripheral blood signatures were similar between groups suggesting that PFAPA and SURF patient tonsils have localized, persistent inflammation, without clinical symptoms. These data suggest that SURF is a heterogenous syndrome on the autoinflammatory disease spectrum.
先天免疫系统的自身炎症性疾病常发生于儿童早期，表现为反复发作的炎症。虽然目前已有 30 多种遗传性发热疾病得到明确的基因定义，但许多患者仍无法明确诊断。许多儿科患者常被归类为周期性发热、口疮性口炎、咽炎和淋巴结炎（PFAPA）综合征患者，尽管不符合诊断标准。在这里，我们将这些患者归类为未分化复发性发热（SURF）综合征，并确定了其与 PFAPA 综合征不同的独特特征。SURF 患者更可能报告恶心、呕吐和腹痛等胃肠道症状，且与 PFAPA 患者相比，按需类固醇治疗的反应不一致。对于这一以前未定义的患者群体，最佳治疗方案仍不确定，医疗和手术治疗主要取决于家长的偏好。SURF 患者中有一部分接受了扁桃体切除术，结果完全缓解。流式细胞术评估显示白细胞群体与 PFAPA 患者不同，CD3+T 细胞数量减少。与 PFAPA 相比，SURF 患者的扁桃体主要表现为白细胞介素-1（IL-1）特征，即使在不发热期间也是如此。两组患者的外周血特征相似，这表明 PFAPA 和 SURF 患者的扁桃体存在局部、持续性炎症，而无临床症状。这些数据表明，SURF 是自身炎症性疾病谱上的一种异质性综合征。
