Clinical Neurosciences (Pediatric Pain Research Group), UCL GOS Institute of Child Health, London, UK; Department of Pediatric Anesthesia and Pain Medicine, Great Ormond Street Hospital NHS Foundation Trust, London, UK.
Department of Pediatric Anesthesia and Pain Medicine, Great Ormond Street Hospital NHS Foundation Trust, London, UK.
J Pediatr. 2019 Mar;206:217-224.e9. doi: 10.1016/j.jpeds.2018.10.024. Epub 2018 Nov 9.
To evaluate the clinical features of erythromelalgia in childhood associated with gain-of-function SCN9A mutations that increase activity of the Na1.7 voltage-gated sodium channel, we conducted a systematic review of pediatric presentations of erythromelalgia related to SCN9A mutations, and compared pediatric clinical presentations of symptomatic erythromelalgia, with or without SCN9A mutations.
PubMed, Embase, and PsycINFO Databases were searched for reports of inherited erythromelalgia in childhood. Clinical features, management, and genotype were extracted. Case notes of pediatric patients with erythromelalgia from the Great Ormond Street Hospital Pain Service were reviewed for clinical features, patient-reported outcomes, and treatments. Children aged over 10 years were recruited for quantitative sensory testing.
Twenty-eight publications described erythromelalgia associated with 15 different SCN9A gene variants in 25 children. Pain was severe and often refractory to multiple treatments, including nonspecific sodium channel blockers. Skin damage or other complications of cold immersion for symptomatic relief were common (60%). SCN9A mutations resulting in greater hyperpolarizing shifts in Na1.7 sodium channels correlated with symptom onset at younger ages (P = .016). Variability in reporting, and potential publication bias toward severe cases, limit any estimations of overall prevalence. In our case series, symptoms were similar but comorbidities were more common in children with SCN9A mutations. Quantitative sensory testing revealed marked dynamic warm allodynia.
Inherited erythromelalgia in children is associated with difficult-to-manage pain and significant morbidity. Standardized reporting of outcome and management in larger series will strengthen identification of genotype-phenotype relationships. More effective long-term therapies are a significant unmet clinical need.
评估与增加 Na1.7 电压门控钠离子通道活性的功能获得性 SCN9A 突变相关的儿童红斑性肢痛症的临床特征，我们对与 SCN9A 突变相关的红斑性肢痛症的儿科表现进行了系统评价，并比较了有或没有 SCN9A 突变的症状性红斑性肢痛症的儿科临床表现。
在 PubMed、Embase 和 PsycINFO 数据库中搜索有关儿童遗传性红斑性肢痛症的报告。提取临床特征、治疗方法和基因型。对大奥蒙德街医院疼痛科的儿童红斑性肢痛症病例进行回顾性分析，评估其临床特征、患者报告的结局和治疗方法。对年龄超过 10 岁的儿童进行定量感觉测试。
28 篇文献描述了与 25 名儿童的 15 种不同 SCN9A 基因突变相关的红斑性肢痛症。疼痛剧烈，且对多种治疗方法（包括非特异性钠离子通道阻滞剂）往往具有抗性。为缓解症状而进行的皮肤损伤或其他寒冷浸浴并发症较为常见（60%）。导致 Na1.7 钠离子通道发生更大超极化偏移的 SCN9A 突变与年龄较小的症状发作相关（P = .016）。由于报告的变异性和对严重病例的潜在发表偏倚，限制了对总体患病率的任何估计。在我们的病例系列中，症状相似，但患有 SCN9A 突变的儿童合并症更为常见。定量感觉测试显示明显的动态热感觉异常。
儿童遗传性红斑性肢痛症与难以治疗的疼痛和显著的发病率有关。在更大系列中对结局和管理进行标准化报告将有助于确定基因型-表型关系。更有效的长期治疗是一个重大的未满足的临床需求。
