Department of Pediatric Nephrology and Rheumatology, Medical Faculty, Dokuz Eylül University, Izmir, Turkey.
Department of Pediatric Nephrology, Medical Faculty, Dokuz Eylül University, Izmir, Turkey.
Rheumatol Int. 2021 Jan;41(1):183-188. doi: 10.1007/s00296-019-04389-3. Epub 2019 Jul 19.
Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome and familial Mediterranean fever (FMF) are considered as inflammasome disorders associated with uncontrolled interleukin (IL)-1β production. Anti-IL1 agents are used in colchicine-resistant cases of FMF. Increase in pro-inflammatory mediators even between febrile attacks in PFAPA suggests that anti-IL1 treatment might be beneficial in these patients. We describe a child presenting with recurrent, self-limited febrile attacks at 1 year of age who was diagnosed as FMF being heterozygous for M694 V mutation. Her clinical findings were only controlled by the addition of canakinumab (2 mg/kg/8 week) to colchicine treatment. However, she developed typical PFAPA attacks during this treatment at 3 years of age. We conducted a literature search focusing on English articles with keywords including PFAPA, anakinra, canakinumab, and rilonacept. Five children and one adult patient with PFAPA were found and evaluated. Anakinra was reported to abort PFAPA attacks in children, while the adult patient first responded and then became resistant to anakinra. Canakinumab was effective in preventing febrile attacks in this patient. Failure of canakinumab to prevent PFAPA attacks in our case may arise from the differences in the pathophysiology of PFAPA and FMF. Thus, further experience with higher doses or shorter intervals of canakinumab is needed in children with PFAPA.
周期性发热、口疮性口炎、咽炎和颈淋巴结炎（PFAPA）综合征和家族性地中海热（FMF）被认为是与白细胞介素（IL）-1β失控产生相关的炎症小体疾病。抗 IL-1 药物用于 FMF 的秋水仙碱耐药病例。PFAPA 中甚至在发热发作之间促炎介质的增加表明抗 IL-1 治疗可能对这些患者有益。我们描述了一名 1 岁时出现反复发作、自限性发热发作的儿童，被诊断为杂合 M694V 突变的 FMF。她的临床发现仅通过在秋水仙碱治疗的基础上加用卡那单抗（2mg/kg/8 周）得到控制。然而，她在 3 岁时接受治疗时出现了典型的 PFAPA 发作。我们进行了一项文献检索，重点关注包含 PFAPA、阿那白滞素、卡那单抗和 rilonacept 等关键词的英文文章。发现并评估了 5 名儿童和 1 名成人 PFAPA 患者。阿那白滞素被报道可终止儿童的 PFAPA 发作，而该成年患者最初有反应，然后对阿那白滞素产生耐药性。卡那单抗在该患者中预防发热发作有效。卡那单抗在我们的病例中未能预防 PFAPA 发作可能是由于 PFAPA 和 FMF 的病理生理学差异所致。因此，在患有 PFAPA 的儿童中需要进一步使用更高剂量或更短间隔的卡那单抗的经验。
