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Abstract：
BACKGROUND: Cryopyrin-associated periodic syndrome (CAPS) is a life-long, autoinflammatory disease associated with a gain-of-function mutation in the nucleotide-binding domain, leucine-rich repeat family, pyrin domain containing 3 (NLRP3) gene, which result in uncontrolled production of IL-1β and chronic inflammation. Chronic infantile neurologic cutaneous and articular (CINCA) syndrome/neonatal-Onset multisystem inflammatory disease (NOMID) is the most severe form of CAPS. Although the first symptoms may be presented at birth, there are few reports on the involvement of the placenta and umbilical cord in the disease. Therefore, we present herein a preterm case of CINCA/NOMID syndrome and confirms intrauterine-onset inflammation with conclusive evidence by using fetal and placental histopathological examination.
METHODS: The female patient was born at 33weeks of gestation by emergency caesarean section and weighted at 1,514 g. The most common manifestations of CINCA/NOMID syndrome including recurrent fever, urticarial rash, and ventriculomegaly due to aseptic meningitis were presented. She also exhibited atypical symptoms such as severe hepatosplenomegaly with cholestasis. The genetic analysis of NLRP3 revealed a heterozygous c.1698 C > G (p.Phe566Leu) mutation, and she was diagnosed with CINCA/NOMID syndrome. Further, a histopathological examination revealed necrotizing funisitis, mainly inflammation of the umbilical artery, along with focal neutrophilic and lymphocytic villitis.
CONCLUSIONS: The necrotizing funisitis, which only involved the artery, was an unusual observation for chorioamnionitis. These evidences suggest that foetal inflammation, probably due to overproduction of IL-1β, caused tissue damage in utero, and the first symptom of a newborn with CINCA/NOMID.
METHODS: The female patient was born at 33weeks of gestation by emergency caesarean section and weighted at 1,514 g. The most common manifestations of CINCA/NOMID syndrome including recurrent fever, urticarial rash, and ventriculomegaly due to aseptic meningitis were presented. She also exhibited atypical symptoms such as severe hepatosplenomegaly with cholestasis. The genetic analysis of NLRP3 revealed a heterozygous c.1698 C > G (p.Phe566Leu) mutation, and she was diagnosed with CINCA/NOMID syndrome. Further, a histopathological examination revealed necrotizing funisitis, mainly inflammation of the umbilical artery, along with focal neutrophilic and lymphocytic villitis.
CONCLUSIONS: The necrotizing funisitis, which only involved the artery, was an unusual observation for chorioamnionitis. These evidences suggest that foetal inflammation, probably due to overproduction of IL-1β, caused tissue damage in utero, and the first symptom of a newborn with CINCA/NOMID.
摘要：
背景：Cryopyrin相关的周期性综合征（CAPS）是一种终身，与核苷酸结合域功能获得突变相关的自身炎症性疾病，富含亮氨酸的重复家族，含Pyrin结构域3(NLRP3)基因,这导致IL-1β的不受控产生和慢性炎症。慢性婴儿神经皮肤和关节（CINCA）综合征/新生儿发作多系统炎症性疾病（NOMID）是CAPS的最严重形式。虽然最初的症状可能在出生时出现，关于该疾病涉及胎盘和脐带的报道很少。因此,我们在此介绍了CINCA/NOMID综合征的早产病例,并通过使用胎儿和胎盘组织病理学检查证实了宫内发作的炎症。
方法：该女性患者在妊娠33周时通过紧急剖腹产出生，体重为1,514g。CINCA/NOMID综合征最常见的表现包括反复发热，荨麻疹,出现了无菌性脑膜炎引起的脑室增宽。她还表现出非典型症状，例如严重的肝脾肿大伴胆汁淤积。NLRP3的遗传分析显示杂合c.1698C>G（p。Phe566Leu)突变,她被诊断为CINCA/NOMID综合征。Further,组织病理学检查显示坏死性真菌，主要是脐动脉的炎症，以及局灶性嗜中性粒细胞和淋巴细胞性绒毛膜炎。
结论：坏死性真菌，只涉及动脉，是绒毛膜羊膜炎的一个不寻常的观察结果。这些证据表明胎儿炎症，可能是由于IL-1β的过量产生，导致子宫内组织损伤，和新生儿出现CINCA/NOMID的首发症状。
方法：该女性患者在妊娠33周时通过紧急剖腹产出生，体重为1,514g。CINCA/NOMID综合征最常见的表现包括反复发热，荨麻疹,出现了无菌性脑膜炎引起的脑室增宽。她还表现出非典型症状，例如严重的肝脾肿大伴胆汁淤积。NLRP3的遗传分析显示杂合c.1698C>G（p。Phe566Leu)突变,她被诊断为CINCA/NOMID综合征。Further,组织病理学检查显示坏死性真菌，主要是脐动脉的炎症，以及局灶性嗜中性粒细胞和淋巴细胞性绒毛膜炎。
结论：坏死性真菌，只涉及动脉，是绒毛膜羊膜炎的一个不寻常的观察结果。这些证据表明胎儿炎症，可能是由于IL-1β的过量产生，导致子宫内组织损伤，和新生儿出现CINCA/NOMID的首发症状。
