Phenotype, genotype, and sustained response to anakinra in 22 patients with autoinflammatory disease associated with CIAS-1/NALP3 mutations
Phenotype, genotype, and sustained response to anakinra in 22 patients with autoinflammatory disease associated with CIAS-1/NALP3 mutations
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DOI：
10.1001/archderm.142.12.1591
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发表时间：
2006-12-01
影响因子：
--
通讯作者：
Hawkins, Philip N.
中科院分区：
文献类型：
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作者：
Leslie, Kieron S.;Lachmann, Helen J.;Hawkins, Philip N.
目的：描述多系统慢性炎症表型、皮肤病理学特征和对白细胞介素I受体拮抗剂治疗的反应CIAS-1/NALP 3基因突变患者的阿那白滞素（anakinra）。设计：回顾性审查病历和评估组织学结果。设置：国家淀粉样变性中心，伦敦，和荨麻疹三级转诊诊所。患者：来自13个家族的22名个体与CIAS-1/NALP 3 mutations.Main Outcome Measures：Phenotype，genotype，skin histologic findings，and response to treatment with anakinra.Results：5个杂合错义突变在CIAS-1/NALP 3中被鉴定。皮肤组织学检查发现明显的血管扩张和嗜酸性浸润，累及小血管和小汗腺。在未治疗的患者中存在强烈炎症的血清学证据，中位血清淀粉样蛋白A蛋白和C反应蛋白水平分别为141和38 mg/L。15例患者接受阿那白滞素治疗长达39个月，所有患者均达到血清学缓解，发热、皮疹、结膜炎和风湿症状完全消退，无任何不良反应。6例患者患有AA（反应性系统性）淀粉样变性，其中2人死于肾衰竭并发症之前白细胞介素1抑制治疗可用; 1例患者接受肾移植，并保持临床良好服用阿那白滞素，并在其余3例患者，阿那白滞素治疗导致他们的肾病综合征缓解。阿那白滞素治疗耐受性良好，对这些CIAS-1/NALP 3突变患者的皮肤病和风湿性表现具有持续疗效。该治疗还导致所有受累患者AA淀粉样变性相关肾病综合征消退。
Objective: To characterize the multisystem chronic inflammatory phenotype, dermatopathologic features, and response to therapy with interleukin I receptor antagonist (anakinra) in patients with mutations in the CIAS-1/NALP3 gene.Design: Retrospective review of medical records and evaluation of histologic findings.Setting: The National Amyloidosis Centre, London, and a tertiary referral clinic for urticaria.Patients: Twenty-two individuals from 13 families with autoinflammatory disease associated with CIAS-1/ NALP3 mutations.Main Outcome Measures: Phenotype, genotype, skin histologic findings, and response to treatment with anakinra.Results: Five heterozygous missense mutations were identified in CIAS-1/NALP3. Skin histologic findings revealed marked vascular dilatation and neutrophilic infiltration involving small vessels and eccrine glands. Serologic evidence of intense inflammation was present in untreated patients, with median serum amyloid A protein and C-reactive protein levels of 141 and 38 mg/L, respectively. Fifteen patients received anakinra for up to 39 months, all of whom achieved serologic remission and complete resolution of fever, rash, conjunctivitis, and rheumatic symptoms, without any adverse effects. Six patients had AA (reactive systemic) amyloidosis, 2 of whom died of renal failure complications before interleukin 1-inhibiting therapy was available; 1 patient underwent renal transplantation and remains clinically well taking anakinra, and in the remaining 3 patients, anakinra therapy resulted in remission of their nephrotic syndrome.Conclusions: Anakinra therapy was well tolerated and has sustained efficacy on dermatologic and rheumatic manifestations in these patients with CIAS-1/NALP3 mutations. This treatment also resulted in resolution of AA amyloidosis-associated nephrotic syndrome in all affected patients.