WHAT'S KNOWN ON THIS SUBJECT: Sleep disturbance affects 47% to 60% of children with atopic dermatitis and is a leading cause of impaired quality of life for the patients and their family. WHAT THIS STUDY ADDS:Sleep disturbance in children with atopic dermatitis can be predicted by a Scoring Atopic Dermatitis index of $48.7, and lower nocturnal melatonin secretion might play a role in the pathophysiology. abstract BACKGROUND AND OBJECTIVES: Sleep disturbance is common in patients with atopic dermatitis (AD). However, studies have largely been questionnaire-based, and the pathophysiology remains unclear. The aims of this study were to determine objective characteristics of sleep disturbance in children with AD and explore contributing factors and clinical predictors.METHODS: Sleep parameters were measured by actigraphy and polysomnography in 72 patients with AD and 32 controls ages 1 to 18 years. Urinary 6-sulfatoxymelatonin levels, serum cytokines, and total and allergen-specific immunoglobulin E (IgE) levels were also measured. RESULTS:The patients with AD had significantly reduced sleep efficiency, longer sleep onset latency, more sleep fragmentation, and less nonrapid eye movement sleep. Results from actigraphy correlated well with those from polysomnography. The AD disease severity was associated with sleep disturbance (r = 0.5520.7), and a Scoring Atopic Dermatitis index of $48.7 predicted poor sleep efficiency with a sensitivity of 83.3% and a specificity of 75% (area under the curve = 0.81, P = .001). Lower nocturnal melatonin secretion was significantly associated with sleep disturbance in the patients with AD. Other correlates of sleep disturbance included pruritus, scratching movements, higher total serum IgE levels, and allergic sensitization to dust mite and staphylococcal enterotoxins. CONCLUSIONS:Poor sleep efficiency is common in children with AD and can be predicted by the Scoring Atopic Dermatitis index. Melatonin and IgE might play a role in the sleep disturbance. Further studies are required to explore the mechanisms and clinical implications, and actigraphy could serve as a useful evaluating tool. Atopic dermatitis (AD) is a common chronically relapsing pruritic inflammatory skin disease. 1 Disturbed sleep is frequently reported by the patients and their family and is a major factor leading to an impaired quality of life. [2][3][4] Sleep disturbance can have many negative consequences, including impaired neurocognitive function, higher rates of behavioral problems, and changes in mood. 5,6 Therefore, the recognition and proper management of sleep disturbance should be an important issue in AD.The sleep disturbance in AD might be due to the pruritus and scratching movements during sleep, 7-10 but it is likely that other factors are involved. 11 Melatonin is a hormone secreted by the pineal gland that is essential for regulating the circadian rhythm. 12 Dysfunction in the diurnal secretion of melatonin in patients with AD has been reported, 13 but its association with their sleep disturbance has...

SummaryOur purpose was to determine whether numbers of CD4 + CD25 + T [T regulatory (Treg)] cells and mRNA expression of functional molecules of Treg are related to airway allergy and disease severity in 51 paediatric patients with allergic rhinitis or bronchial asthma and 47 healthy controls. Surface markers were evaluated with flow cytometry, and mRNA was determined with realtime polymerase chain reaction. Children with allergic disease had fewer CD4 + CD25 + T cells (8·49% Ϯ 2·41% versus 9·58% Ϯ 2·43%, P < 0·05) and CD4 + CD25 hi T cells (1·32% Ϯ 0·68% versus 1·70% Ϯ 0·68%, P < 0·01) than control subjects. Numbers of CD4 + CD25 + and CD4 + CD25 hi T lymphocytes were higher in children with persistent allergic rhinitis and/or moderatesevere bronchial asthma than in those with respective milder disease. The number of Treg cells was correlated positively with total immunoglobulin E level. The mRNA expression of forkhead box P3 (FoxP3) was increased in moderate-severe versus mild asthma (2·93 Ϯ 0·38 versus 1·60 Ϯ 0·31, P < 0·01). Patients with moderate-severe bronchial asthma also had increased mRNA expression of interleukin (IL)-10 compared with patients with mild asthma (15·24 Ϯ 4·07 versus 3·77 Ϯ 2·18, P < 0·01). The suppressive function of Treg cells from patients with more severe asthma was competent in vitro. On average, decreased numbers of Treg cells in children with allergic airway disease might represent a defect of the Treg population. With increased expression of FoxP3 and IL-10 in Treg from patients with relatively severe allergic disease, adaptive and functional Treg might be generated in response to aggravated atopy and disease severity.

IMPORTANCE 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. OBJECTIVE 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. INTERVENTIONS 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. MAIN OUTCOMES AND MEASURES 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. RESULTS 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. CONCLUSIONS AND RELEVANCE Melatonin supplementation is a safe and effective way to improve the sleep-onset latency and disease severity in children with AD. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01638234

Summary CD4+ CD25+ regulatory T cells (Tregs) are critical in maintaining self‐tolerance and preventing organ‐specific autoimmunity. Their role in paediatric systemic lupus erythematosus (SLE), an autoimmune disease characterized by inappropriate regulation of hyperactivated B and T cells, has not been clearly defined. Using flow cytometry to determine cell populations and real‐time polymerase chain reaction to assay mRNA expression for FOXP3, CTLA‐4, and GITR, we characterized CD4+ CD25+ T cells in paediatric SLE patients and healthy subjects. The frequency of CD4+ CD25+ Tregs was significantly decreased in patients with active SLE compared with patients with inactive SLE and with controls (7·27% ± 2·50%, 9·59% ± 2·80% and 9·78% ± 2·11%, respectively; P = 0·027 and P < 0·001, respectively), and was inversely correlated with disease activity, as assessed with the Systemic Lupus Erythematosus Disease Activity Index 2000 scores (r = −0·59, P = 0·001) and serum anti‐double‐stranded DNA levels (r = −0·65, P < 0·001). Our preliminary investigations found elevated surface expression of GITR in CD4+ CD25+ T cells, elevated mRNA expression of CTLA‐4 in CD4+ T cells and higher amounts of mRNA expression for FOXP3 in CD4+ cells in patients with active SLE compared with patients with inactive disease and controls. We demonstrated reduced CD4+ CD25+ Treg levels were inversely correlated with disease activity, indicating a defective Treg population in paediatric SLE patients. The differences in the expression of FOXP3, CTLA‐4 and GITR imply the possible role of CD4+ Tregs in the pathogenesis of SLE.

Insurance claim data provide useful information on the epidemiology of HSP in Taiwan. Childhood HSP in Taiwan, with an incidence of 12.9 per 100 000 children, occurs commonly in autumn and winter; and at the age of 5 to 6 yr. The characteristics presented in this study may provide valuable data for understanding and further studies of HSP.