沙利度胺致小儿炎症性肠病患者周围神经病的危险因素及转归。

Risk Factors and Outcomes of Thalidomide-induced Peripheral Neuropathy in a Pediatric Inflammatory Bowel Disease Cohort.

机构信息

*Pediatric Gastroenterology, Institute for Maternal and Child Health, IRCCS "Burlo Garofolo," Trieste, Italy; †Department of Life Sciences, University of Trieste, Trieste, Italy; ‡Clinical Epidemiology and Public Health Research Unit, Institute for Maternal and Child Health, IRCCS "Burlo Garofolo," Trieste, Italy; §Pediatric Gastroenterology Unit, Institute "Giannina Gaslini," Genoa, Italy; ‖Neuropsychiatry Unit, Institute "Giannina Gaslini," Genoa, Italy; ¶Pediatric Gastroenterology and Cystic Fibrosis Unit, University of Messina, Messina, Italy; **Department of Sciences for Woman and Child Health, University of Florence, Meyer Children Hospital, Florence, Italy; ††Pediatric Department, Children's Hospital "V. Buzzi" Milan, Italy; ‡‡Pediatric Gastroenterology and Hepatology, University of Pisa, Pisa, Italy; §§Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy; and ‖‖Pediatric Neurology, Institute for Maternal and Child Health, IRCCS "Burlo Garofolo," Trieste, Italy.

出版信息

Inflamm Bowel Dis. 2017 Oct;23(10):1810-1816. doi: 10.1097/MIB.0000000000001195.

DOI:10.1097/MIB.0000000000001195

PMID:28817461

Abstract

BACKGROUND

Thalidomide is an effective therapy in children with inflammatory bowel disease refractory to standard treatments, but thalidomide-induced peripheral neuropathy (TiPN) limits its long-term use. We aimed to investigate the risk factors and the outcome of TiPN in children with inflammatory bowel disease.

METHODS

Within a retrospective multicenter cohort study, we evaluated prevalence and evolution of TiPN. Clinical data and candidate genetic profiles of patients with and without TiPN were compared with detect predisposing factors.

RESULTS

One hundred forty-two patients were identified. TiPN was found in 72.5% of patients (38.7% clinical and instrumental alterations, 26.8% exclusive electrophysiological anomalies, and 7.0% exclusive neurological symptoms). Median TiPN-free period of treatment was 16.5 months; percentage of TiPN-free patients was 70.0% and 35.6% at 12 and 24 months of treatment, respectively. The risk of TiPN increased depending on the mean daily dose (50-99 mg/d adjusted hazard ratio 2.62; 95% confidence interval [CI], 1.31-5.21; 100-149 mg/d adjusted hazard ratio 6.16; 95% CI, 20.9-13.06; >150 mg/d adjusted hazard ratio 9.57; 95% CI, 2.6-35.2). Single nucleotide polymorphisms in ICAM1 (rs1799969) and SERPINB2 (rs6103) genes were found to be protective against TiPN (odds ratio 0.15; 95% CI, 0.03-0.82 and 0.36; 95% CI, 0.14-0.88, respectively). TiPN was the cause of drug suspension in 41.8% of patients. Clinical symptoms resolved in 89.2% of cases, whereas instrumental alteration persisted in more than half of the patients during a short follow-up.

CONCLUSIONS

In children with inflammatory bowel disease, TiPN is common but mild and generally reversible. Cumulative dose seems to be the most relevant risk factor, whereas polymorphisms in genes involved in neuronal inflammation may be protective.

摘要

背景

沙利度胺对标准治疗无效的儿童炎症性肠病是一种有效的治疗方法，但沙利度胺诱导的周围神经病（TiPN）限制了其长期使用。我们旨在研究儿童炎症性肠病中 TiPN 的危险因素和结果。

方法

在回顾性多中心队列研究中，我们评估了 TiPN 的患病率和演变。比较了有和没有 TiPN 的患者的临床数据和候选遗传特征，以发现易患因素。

结果

共确定了 142 名患者。TiPN 在 72.5%的患者中发现（38.7%的临床和仪器改变，26.8%的单纯电生理学异常，7.0%的单纯神经症状）。TiPN 无治疗期的中位数为 16.5 个月；治疗 12 个月和 24 个月时 TiPN 无治疗患者的比例分别为 70.0%和 35.6%。TiPN 的风险随着平均日剂量的增加而增加（50-99mg/d 调整后的危险比为 2.62；95%置信区间[CI]，1.31-5.21；100-149mg/d 调整后的危险比为 6.16；95%CI，20.9-13.06；>150mg/d 调整后的危险比为 9.57；95%CI，2.6-35.2）。ICAM1（rs1799969）和 SERPINB2（rs6103）基因的单核苷酸多态性被发现可预防 TiPN（比值比 0.15；95%CI，0.03-0.82 和 0.36；95%CI，0.14-0.88）。TiPN 是 41.8%的患者停药的原因。89.2%的临床症状得到缓解，而在短时间随访期间，超过一半的患者存在仪器改变。