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The Relationship of Sleep and Urine Levels of Melatonin in Children with Atopic Dermatitis
atopic dermatitis,melatonin,SCORAD index,IDQOL,CDLQI,DFI,Actigraphy,
|Publication Year :||2012|
本研究之對象為1~16歲異位性皮膚炎的病童，另收集年齡相仿的健康孩童做為對照組。異位性皮膚炎的疾病嚴重度以SCORAD index作評分，並請病童或照顧者填寫皮膚炎生活品質（IDQOL、ＣDLQI）及家庭衝擊（DFI）問卷。所有受試者必須在檢查的當晚於睡覺時配戴Actigraph在非慣用手上，以評估睡眠狀態及夜間手腕的活動情形，並於睡眠檢查的隔天清晨起床時收集尿液10∼15c.c，再以 enzyme immunoassay的方法測量尿液中退黑激素代謝物6-hydroxymelatonin sulfate的濃度，之後比較兩組的睡眠品質、搔抓頻率和退黑激素分泌是否有差異，並分析病童的Actigraphy測量結果、SCORAD、問卷分數、以及退黑激素之間的相關性。
我們收集了26位異位性皮膚炎的病童和28位健康的對照組，平均年齡分別為7.1 ± 4.4及8.4 ± 3.9歲。和健康對照組相比，異位性皮膚炎病童的入睡所需時間較長，睡眠效率較差，睡覺時搔抓的動作較頻繁，且疾病嚴重度與睡眠效率呈明顯負相關性、和搔癢活動的頻率則有顯著正相關。病童的生活品質及家庭衝擊問卷評分和Actigraphy的測量結果皆無顯著相關性，不過生活品質問卷的分數與疾病嚴重度有顯著正相關。至於睡眠和搔癢程度的相關性，病童Actigraphy的睡眠及搔抓動作測量結果呈顯著負相關，分析SCORAD的主觀評分項目也發現失眠程度和搔癢嚴重度有明顯的正相關。另外我們也評估以主觀及客觀方法測量的睡眠及搔癢結果是否一致，發現Actigraphy所測得的睡眠效率及搔抓活動分別與SCORAD的失眠及搔癢程度主觀評分有顯著相關。在退黑激素的比較方面，異位性皮膚炎病童的尿中退黑激素濃度和健康孩童並無差異，和Actigraphy的檢查結果以及疾病嚴重度亦無明顯相關性。
Background and Objectives
Atopic dermatitis (AD) is a chronic allergic skin disease with significant costs and morbidity to patients and their families. The pathogenesis is proposed to be contributed by multi-factors, including inherited genetic susceptibility, environmental triggers and allergens, abnormal immune response, and skin barrier disorder. The incidence of AD is increasing world-wide, with 10-20% among pediatric patients and 2-3% among adults. Sleep disturbance is one of the most common complaints among these patients, which can result in daytime fatigue, mood disorder, reduced behavior and neurocognitive functioning, and compromised quality of life.
Recent studies have advanced our understanding that allergic inflammation triggers neuronal dysfunction, thereby modulating inflammatory responses through neuromediators in affected tissues including the skin. Melatonin is a neurohormone produced mainly by the pineal gland and has been shown to influence many biological functions, including hypnotic effect and modulating immune cell production and action. It remains unknown that if melatonin plays a role in skin inflammation and sleep problems in patients with AD. The purpose of our study was to compare the sleep condition, nocturnal wrist movements and urine levels of melatonin between pediatric patients with AD and healthy controls, and to further correlate the sleep condition with urine concentration of melatonin, disease severity and quality of life in AD patients.
Materials and Methods
Participants and Study design
Children who aged between 1 and 16 years and visited the pediatric allergy clinic of National Taiwan University Hospital between May and October 2011 with a diagnosis of atopic dermatitis were recruited in this study. Patients were excluded if they: had co-morbidities of other major systemic diseases; had received therapy for insomnia within 1 month before entering this study; had received systemic steroid or immunosuppressant medication 1 month prior to the study. Age-matched healthy children were enrolled as controls.
The eczema of disese of children with AD patients was assessed using the Severity sCORing of Atopic Dermatitis (SCORAD) index system (Fig. 1), which combines extent, intensity and subjective symptoms. The rule of nine is used to estimate the extent of involvement of total body surface area (TBSA) by eczema (Fig. 2). The six intensity items included erythema, edema/population, oozing/crust, excoriation, lichenification and dryness. The subjective components in SCORAD index consist of questions to sleep loss and pruritus, and children with AD or their caretakers were asked to record their responses to each question on a 10-cm horizontal visual analogue scale.
Children with AD or their caretakers were instructed to complete the 10-item questionnaires of Infants’(IDQOL, Table 1) or Children’s (CDLQI, Table 2) Dermatology Life Quality Index based on age younger or older than 4 years old. The caretakers of children with AD were asked to complete the 10-item Dermatitis Family Impact questionnaire (DFI) (Table 3) on which they quantified the impact of AD on family.
We assess the sleep condition and wrist movements of all participants by Actigraphy, which is a watch-shaped wrist-worn accelerometer and can record the integration of intensity, amount and duration of wrist movements (Fig. 3). Participants wore the Actigraph on their non-dominant wrist through one night. Actigraph data used for this investigation included onset latency (time to sleep onset), sleep efficiency (proportion of time in bed spent asleep), and % mobile (percentage of total mobile time in the total recording time).
After an overnight sleep measure with the Actigraph, 10~15 c.c. first morning urine output was collected on the next day from each volunteer. Urinary levels of melatonin primary metabolite, 6-hydroxymelatonin sulfate, were determined in enzyme immunoassay (ELISA) with commercial ELISA kits.
The Actigraph measures and the urine concentrations of melatonin were compared between patients and healthy controls. Correlations among sleep quality, SCORAD, and questionnaires scores were analyzed. Associations between the Actigraph measures and the subjective elements about sleep and itch were determined. The relation of urine levels of melatonin to Actigraph recordings and SCORAD scores were also investigated.
The Actigraphy data and urine levels of melatonin were compared by the Student’s t test between AD group and controls. Correlation among Actigraph measures, urine levels of melatonin, SCORAD and questionnaires scores were made using Spearman nonparametric correlation coefficients. Results were considered significant if the p value was less than 0.05. All of the statistical analyses were performed with SPSS version 13.0 for Windows (SPSS Inc., Chicago, IL, USA).
The patient group consisted of 12 males and 14 females (mean ± SD age 7.1 ± 4.4 yr). Twenty eight normal children (14 males, 14 females, mean ± SD age 8.4 ± 3.9 yr) served as controls. The median (interquartile range) SCORAD was 29.3 (19.975-40.9).
Results of Actigraphy sleep measures
A significantly longer sleep latency (50.69 ± 33.99 vs. 22.84 ± 16.90, p = 0.001), lower sleep efficiency (73.42 ± 9.72 vs. 83.09 ± 7.16, p < 0.001) and more frequent wrist movements (% mobile, 11.58 ± 7.25 vs. 6.66 ± 3.02, p = 0.003) in the patient group than that of the control group were found (Table 4).
Results of urine melatonin levels
urine melatonin levels, there was no significance between the two groups (170.89 ± 120.91 ng/ml, n=20 in the AD group vs. 133.29 ± 94.07 ng/ml, n=28 in the control group, p = 0.232) (Fig. 4).
Correlations among Actigraphy recordings, SCORAD and questionnaires scores
The result of a negative correlation between sleep latency and the SCORAD score was surprising, but the relation between them was poor (-0.019, p = 0.926) (Table 5). The SCORAD score was significantly negatively correlated with sleep efficiency (-0.438, p = 0.025) and positively correlated with wrist activities (% mobile) (0.551, p = 0.004) (Table 5). In respect of questionnaires, there was little relation between the Dermatology Life Quality Index (DLQI includes IDQOL and CDLQI) and the Actigraph parameters, but the DLQI was significantly correlated with the SCORAD score (0.567, p = 0.003) (Table 6). The Dermatitis Family Impact (DFI) did not associate either with the Actigraph measures or the SCORAD scores (Table 5, 6).
Relation between sleep and pruritus measures
We investigated the relationship between sleep and pruritus measures in children with AD. The Actigraph sleep efficiency score was significantly inversely related to wrist movement score (-0.605, p = 0.0011) (Fig. 5). The sleep self-rating also correlated well with itch self-rating (0.623, p = 0.0007) (Fig. 6).
Relation of objective measures to self-reported sleep and pruritus
To determine how objectively measured sleep efficiency and wrist activity compare with self-rated sleep and itch, associations between each measure were examined. The Actigraph sleep efficiency was well-correlated with self-reported sleep loss (-0.662, <0.001) (Fig. 7), and the Actigraph wrist movements (% mobile) was significantly related to self-reported itch (0.515, p = 0.007) (Fig. 8).
Correlation of urine melatonin levels with Actigraphy recordings and SCORAD
Urine levels of melatonin did not correlate with either the Actigraph measures or the SCORAD scores (Table 7).
This study demonstrated that sleep is significantly compromised in AD subjects. Children with AD spent more time to fall asleep, slept more poorly, and had more nocturnal scratching than the control subjects. The results of our study also revealed that decreased sleep efficiency and increased scratching were associated with increasing disease severity. The quality of life of AD children was significantly inversely correlated with disease severity. The relation between sleep and pruritus were straightforward, and the patients’perception about sleep and itch correlated well with the objective
measures. In the case of nocturnal urine levels of melatonin, there was no significant difference between the AD group and the control group. The relation between melatonin concentrations and sleep quality was imperfect, and the association between melatonin levels and disease activity was also not significant.
Our study provides more detailed and accurate information about sleep and builds an evidence base for further studies to investigate the role of melatonin in AD. Additional studies should also be conducted to direct somnolent therapeutic guidelines for children of AD.
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