Bardet Juliette, Laverdure Noémie, Fusaro Mathieu, Picard Capucine, Garnier Lorna, Viel Sébastien, Collardeau-Frachon Sophie, Guillebon Jean-Marie De, Durieu Isabelle, Casari-Thery Clémence, Mortamet Guillaume, Laurent Audrey, Belot Alexandre
Pediatric Nephrology, Rheumatology, Dermatology Unit, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, 69677 Bron, France.
Pediatric Hepatology, Gastroenterology and Nutrition Unit, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, 69677 Bron, France.
J Clin Med. 2021 Sep 24;10(19):4369. doi: 10.3390/jcm10194369.
The NLRC4 inflammasome is part of the human immune innate system. Its activation leads to the cleavage of pro-inflammatory cytokines IL-1β and IL-18, promoting inflammation. gain-of-function (GOF) mutations have been associated with early-onset recurrent fever, recurrent macrophagic activation syndrome and enterocolitis. Herein, we describe two new patients with mutations. The first case presented with recurrent fever and vasoplegic syndrome, gut symptoms and urticarial rashes initially misdiagnosed as a severe protein-induced enterocolitis syndrome. The second case had recurrent macrophage activation syndrome (MAS) and shock, suggesting severe infection. We identified two mutations, on exon 4, within the nucleotide-binding protein domain (NBD). After a systematic review of GOF mutations, we highlight the wide spectrum of this disease with a limited genotype-phenotype correlation. Vasoplegic shock was only reported in patients with mutation in the NBD. Diagnosing this new entity combined with gastrointestinal symptoms and vasoplegic shocks is challenging. It mimics severe allergic reaction or sepsis. The plasma IL-18 level and genetic screening are instrumental to make a final diagnosis.
NLRC4炎性小体是人体免疫先天系统的一部分。其激活会导致促炎细胞因子IL-1β和IL-18的裂解，从而促进炎症。功能获得性（GOF）突变与早发性反复发热、反复巨噬细胞活化综合征和小肠结肠炎有关。在此，我们描述了两名携带该突变的新患者。第一例最初表现为反复发热和血管麻痹综合征、肠道症状及荨麻疹样皮疹，最初被误诊为严重的蛋白质诱导小肠结肠炎综合征。第二例有反复巨噬细胞活化综合征（MAS）和休克，提示严重感染。我们在核苷酸结合蛋白结构域（NBD）的第4外显子上鉴定出两个该突变。在对该GOF突变进行系统综述后，我们强调了这种疾病的广泛谱系，其基因型与表型的相关性有限。血管麻痹性休克仅在NBD发生突变的患者中被报道。诊断这种合并胃肠道症状和血管麻痹性休克的新疾病具有挑战性。它类似于严重的过敏反应或败血症。血浆IL-18水平和基因筛查有助于做出最终诊断。
