Department of Pediatrics, Taipei City Hospital Renai Branch, Taipei, Taiwan2Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan3School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Department of Pediatrics, Yonghe Cardinal Tien Hospital, New Taipei City, Taiwan.
JAMA Pediatr. 2016 Jan;170(1):35-42. doi: 10.1001/jamapediatrics.2015.3092.
Sleep disturbance is common in children with atopic dermatitis (AD), but effective clinical management for this problem is lacking. Reduced levels of nocturnal melatonin were found to be associated with sleep disturbance and increased disease severity in children with AD. Melatonin also has sleep-inducing and anti-inflammatory properties and therefore might be useful for the management of AD.
To evaluate the effectiveness of melatonin supplementation for improving the sleep disturbance and severity of disease in children with AD.
DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial used a double-blind, placebo-controlled crossover design to study 73 children and adolescents aged 1 to 18 years with physician-diagnosed AD involving at least 5% of the total body surface area. The study was conducted at the pediatric department of a large tertiary care hospital in Taiwan from August 1, 2012, through January 31, 2013. Forty-eight children were randomized 1:1 to melatonin or placebo treatment, and 38 of these (79%) completed the cross-over period of the trial. Final follow-up occurred on April 13, 2013, and data were analyzed from January 27 to April 25, 2014. Analyses were based on intention to treat.
Melatonin, 3 mg/d, or placebo for 4 weeks followed by a 2-week washout period and then crossover to the alternate treatment for 4 weeks.
The primary outcome was AD severity evaluated using the Scoring Atopic Dermatitis (SCORAD) index, with scores ranging from 0 to 103 and greater scores indicating worse symptoms. Secondary outcomes included sleep variables measured by actigraphy, subjective change in sleep and dermatitis, sleep variables measured by polysomnography, nocturnal urinary levels of 6-sulfatoxymelatonin, and serum IgE levels.
After melatonin treatment among the 48 children included in the study, the SCORAD index decreased by 9.1 compared with after placebo (95% CI, -13.7 to -4.6; P < .001), from a mean (SD) of 49.1 (24.3) to 40.2 (20.9). Moreover, the sleep-onset latency shortened by 21.4 minutes after melatonin treatment compared with after placebo (95% CI, -38.6 to -4.2; P = .02). The improvement in the SCORAD index did not correlate significantly with the change in sleep-onset latency (r = -0.04; P = .85). No patient withdrew owing to adverse events, and no adverse event was reported throughout the study.
Melatonin supplementation is a safe and effective way to improve the sleep-onset latency and disease severity in children with AD.
clinicaltrials.gov Identifier: NCT01638234.
患有特应性皮炎 (AD) 的儿童常出现睡眠障碍，但针对这一问题的有效临床治疗方法却很缺乏。研究发现，夜间褪黑素水平降低与儿童 AD 患者的睡眠障碍和疾病严重程度增加有关。褪黑素具有诱导睡眠和抗炎作用，因此可能对 AD 的治疗有用。
评估褪黑素补充剂改善 AD 儿童睡眠障碍和疾病严重程度的效果。
设计、地点和参与者：这是一项随机临床试验，采用双盲、安慰剂对照交叉设计，研究了 73 名年龄在 1 至 18 岁的儿童和青少年，这些患者均经医生诊断患有累及至少 5%体表面积的 AD。研究于 2012 年 8 月 1 日至 2013 年 1 月 31 日在台湾一家大型三级保健医院的儿科部门进行。48 名儿童被随机分为 1:1 接受褪黑素或安慰剂治疗，其中 38 名（79%）完成了试验的交叉期。最终随访于 2013 年 4 月 13 日进行，数据分析于 2014 年 1 月 27 日至 4 月 25 日进行。分析基于意向治疗。
褪黑素 3 mg/d 或安慰剂治疗 4 周，随后洗脱期 2 周，然后交叉至交替治疗 4 周。
主要结局是使用特应性皮炎评分 (SCORAD) 指数评估 AD 严重程度，评分范围为 0 至 103，评分越高表示症状越严重。次要结局包括通过活动记录仪测量的睡眠变量、睡眠和皮炎主观改善情况、通过多导睡眠图测量的睡眠变量、夜间尿液 6-硫酸褪黑素水平和血清 IgE 水平。
在纳入研究的 48 名儿童中，接受褪黑素治疗后，SCORAD 指数与安慰剂相比下降了 9.1（95%CI，-13.7 至 -4.6；P<0.001），从平均（SD）49.1（24.3）降至 40.2（20.9）。此外，与安慰剂相比，接受褪黑素治疗后入睡潜伏期缩短了 21.4 分钟（95%CI，-38.6 至 -4.2；P=0.02）。SCORAD 指数的改善与入睡潜伏期的变化无显著相关性（r=-0.04；P=0.85）。没有患者因不良反应而退出，整个研究过程中没有报告不良反应。
褪黑素补充剂是改善 AD 儿童入睡潜伏期和疾病严重程度的安全有效方法。
clinicaltrials.gov 标识符：NCT01638234。
