Department of Pediatrics, Yokohama City University, Yokohama, Japan.
Pediatr Rheumatol Online J. 2010 Mar 16;8:9. doi: 10.1186/1546-0096-8-9.
CINCA/NOMID is an autoinflammatory disorder characterized by the triad of neonatal onset of cutaneous symptoms, chronic meningitis, and recurrent fever and it presents with distinctive osteoarthropathy, synovitis mainly of the large joints and overgrowth of epimetaphyseal cartilage, particularly of the long bones. The cartilage overgrowth eventually causes osseous overgrowth and deformity that persists beyond skeletal maturity and leads to limb length discrepancy, joint contracture, and early degenerative arthropathy. Autoinflammation in CAPS/NOMID has been proven to derive from excessive release of interleukin-1 (IL-1). It has been well documented that the IL-1 receptor antagonist anakinra (Kineret(R)) helps mitigate systemic inflammation in the disorder. However, a general consensus has not been reached on its beneficial effect on osteoarthropathy. The case of a girl with CINCA/NOMID syndrome who showed dramatic improvement of osteoarthropathy after anakinra treatment is reported. A 4-year-old girl suffered at the age of 10 months from a generalized urticarial skin lesion with recurrent episodes of fever and growth disorder. Blood examination revealed persistent massive neutrophilia, anemia and intense acute phase response. She manifested knee joint swelling with limited ROM when she was 20 months old and was diagnosed as being CINCA/NOMID based on characteristic findings of radiograph despite negative CIAS1 mutation. Radiological examination demonstrated metaphyseal fraying and cupping and widening of the growth plate in the distal femur. MR imaging showed mottled gadolinium enhancement at the chondrosseous junction. Neither significant joint effusion nor synovitis was identified. At 2 years and 7 months of age, anakinra, 2 mg/kg/day given by regular daily subcutaneous injections, was started. A few days after the initiation of the treatment, her clinical symptoms and laboratory findings of active inflammation were promptly alleviated. She was not able to walk unaided prior to the treatment, but she walked independently 1 month after the treatment. Follow-up radiographs and MR imaging showed that growth plate widening and gadolinium enhancement at the chondrosseous junction were less conspicuous. Furthermore, longitudinal growth of the femur and tibia was identified during 20 months of observation.
CINCA/NOMID 是一种自炎症性疾病，其特征为三联征：新生儿期出现皮肤症状、慢性脑膜炎和反复发作的发热，伴有独特的骨关节炎、大关节滑膜炎和骺软骨过度生长，特别是长骨。软骨过度生长最终导致骨过度生长和畸形，这种畸形持续到骨骼成熟后，并导致肢体长度差异、关节挛缩和早期退行性关节炎。CAPS/NOMID 中的自身炎症已被证明源自白细胞介素-1（IL-1）的过度释放。已经有充分的文献证明，白细胞介素-1 受体拮抗剂阿那白滞素（Kineret（R））有助于减轻该疾病的全身炎症。然而，对于其对骨关节炎的有益作用，尚未达成普遍共识。本文报告了一例 CINCA/NOMID 综合征患者在接受阿那白滞素治疗后骨关节炎显著改善的病例。一名 4 岁女孩在 10 个月大时出现全身性荨麻疹样皮疹，反复出现发热和生长障碍。血液检查显示持续大量中性粒细胞增多、贫血和强烈的急性期反应。她在 20 个月大时出现膝关节肿胀，活动范围受限，尽管 CIAS1 突变阴性，仍被诊断为 CINCA/NOMID。影像学检查显示股骨远端骺软骨边缘粗糙、杯口状改变和生长板增宽。磁共振成像显示软骨骨交界处斑驳的钆增强。未见明显关节积液或滑膜炎。在 2 岁 7 个月时，开始每天皮下注射 2 毫克/公斤的阿那白滞素。治疗开始几天后，她的临床症状和活动性炎症的实验室发现迅速缓解。在治疗前她无法独立行走，但治疗后 1 个月她可以独立行走。随访影像学和磁共振成像显示生长板增宽和软骨骨交界处的钆增强不那么明显。此外，在 20 个月的观察期间，还发现了股骨和胫骨的纵向生长。
