Matsubara Tomoyo, Hasegawa Masanari, Shiraishi Masahiro, Hoffman Hal M, Ichiyama Takashi, Tanaka Takeo, Ueda Haruo, Ishihara Tokuhiro, Furukawa Susumu
Department of Pediatrics, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan.
Arthritis Rheum. 2006 Jul;54(7):2314-20. doi: 10.1002/art.21965.
In this report we describe a case of severe chronic infantile neurologic, cutaneous, articular (CINCA) syndrome with a novel G307V cryopyrin mutation and all of the characteristic clinical and laboratory features of this autoinflammatory disease. There was no clear response to standard therapies, including human interleukin-1 (IL-1) receptor antagonist (anakinra) and soluble tumor necrosis factor receptor (etanercept). The patient finally had a partial clinical response (reduction in fever and irritability) and complete laboratory response (improved C-reactive protein and serum amyloid A levels) to humanized anti-IL-6 receptor antibody (MRA), but died from congestive heart failure and interstitial pneumonia 2 months after initiation of therapy. We serially measured the serum cytokine levels and expression of NF-kappaB activation in the patient's peripheral blood mononuclear cells before and during consecutive therapies. Pathologic examination of autopsy specimens was also performed. This case illustrates the continued difficulty in management of patients with CINCA syndrome and the complexity of the inflammatory pathways in this disorder.
在本报告中，我们描述了一例患有新型G307V冷吡啉突变的严重慢性婴儿神经、皮肤、关节（CINCA）综合征病例，该病例具有这种自身炎症性疾病的所有典型临床和实验室特征。对于包括人白细胞介素-1（IL-1）受体拮抗剂（阿那白滞素）和可溶性肿瘤坏死因子受体（依那西普）在内的标准疗法，该病例均无明显反应。该患者最终对人源化抗IL-6受体抗体（MRA）出现了部分临床反应（发热和易怒症状减轻）和完全实验室反应（C反应蛋白和血清淀粉样蛋白A水平改善），但在开始治疗2个月后死于充血性心力衰竭和间质性肺炎。我们在连续治疗前和治疗期间对患者外周血单核细胞中的血清细胞因子水平和NF-κB激活表达进行了连续测量。还对尸检标本进行了病理检查。该病例说明了CINCA综合征患者管理中持续存在的困难以及该疾病炎症途径的复杂性。
