PDF(Pubmed)
Abstract：
Chronic infantile neurological cutaneous articular (CINCA) syndrome is an autoinflammatory disease encompassed in the group of cryopyrin-associated periodic syndromes (CAPS). Patients suffering from CINCA have an elevated risk of developing chronic sequelae, including deforming arthropathy, chronic meningitis, neurodevelopmental delay, and neurosensorial hearing loss. The diagnosis of CINCA presents several difficulties, as the clinical phenotype could be difficult to recognize, and almost half of the patients have negative genetic testing. In this paper, we describe the case of a patient presenting with the typical phenotype of neonatal-onset CINCA who resulted negative for NLRP3 mutations. Based on the clinical judgment, the patient underwent treatment with anti-interleukin-1 (IL-1) agents (anakinra and, later, canakinumab) resulting in a complete clinical and laboratory response that allowed confirmation of the diagnosis. Additional genetic investigations performed after the introduction of anti-IL-1 therapy revealed a pathogenic mosaicism in the NLRP3 gene. After a 12-year follow-up, the patient has not experienced chronic complications. Although genetics is rapidly progressing, this case highlights the importance of early diagnosis of CINCA patients when the clinical and laboratory picture is highly suggestive in order to start the appropriate anti-cytokine treatment even in the absence of a genetic confirmation.
摘要：
慢性婴儿神经皮肤关节（CINCA）综合征是一种自身炎性疾病，涵盖在冷冻比林相关的周期性综合征（CAPS）组中。患有NCA的患者患慢性后遗症的风险升高，包括变形性关节病,慢性脑膜炎,神经发育迟缓,和神经感觉性听力损失。CINCA的诊断存在一些困难，因为临床表型可能很难识别，几乎一半的患者基因检测呈阴性。在本文中,我们描述了1例患者表现为NLRP3突变阴性的典型新生儿-onsetCINCA表型.根据临床判断,患者接受了抗白介素-1（IL-1）药物的治疗（anakinra和，稍后，canakinumab）导致完整的临床和实验室反应，从而可以确认诊断。引入抗IL-1疗法后进行的其他遗传研究显示，NLRP3基因存在致病性镶嵌性。经过12年的随访,患者未出现慢性并发症。虽然遗传学进展迅速,该病例强调了早期诊断CINCA患者的重要性,因为临床和实验室检查结果提示强烈,即使在没有基因证实的情况下也能开始适当的抗细胞因子治疗.
