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...
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
Macrophage activation syndrome (MAS) belongs to secondary hemophagocytic lymphohistiocytosis (HLH) syndrome. It is usually associated with rheumatic diseases. We retrospectively reviewed our hospital's medical records of 102 HLH/MAS patients from the past 20 years. Demographics, clinical data, treatment, and outcomes were analyzed. Among 102 patients, eight patients with underlying juvenile systemic lupus erythematous (two patients), mixed connective tissue disease (one patient), primary anti-phospholipid syndrome (one patient), and systemic type juvenile rheumatoid arthritis (sJRA; four patients) with 13 episodes of MAS were studied. Clinical manifestations of MAS included fever (100 %), hepatosplenomegaly (77 %), lymphadenopathy (38 %), skin rash (62 %), and neurological involvement (31 %). Laboratory features included leukopenia (54 %), anemia (46 %), thrombocytopenia (77 %), jaundice (27 %), hypofibrinogenemia (40 %), decreased erythrocyte sedimentation rate (67 %), and elevated liver enzymes (77 %), lactate dehydrogenase (100 %), ferritin (88 %), triglycerides (91 %), C-reactive protein (85 %), plasma D-dimer (50 %), and hemophagocytosis in bone marrow (83 %). The Epstein-Barr virus and adenovirus infection triggered MAS in two patients with sJRA. Methylprednisolone pulse therapy was effective in two out of three patients, and high-dose intravenous immunoglobulin (IVIG) was effective in two out of six patients. Patients with sJRA responded well to corticosteroids and cyclosporine. Complications included opportunistic infection with Pneumocystis jiroveci, multiple organ failure, and intensive care unit myopathy. The mortality rate was one out of eight (12.5 %). Our results showed that MAS could be fatal and complicate various pediatric autoimmune diseases. It generally has a good response to corticosteroids and IVIG. Prompt recognition and timely treatment can result in good outcomes.
ObjectiveThe incidence and prevalence of juvenile idiopathic arthritis (JIA) vary widely across the world but data in East Asia is lacking. Uveitis is a serious cause of morbidity in JIA. This study aimed to analyze the incidence and prevalence of JIA, and the characteristics of JIA-associated uveitis in Taiwan.MethodsA population-based cohort study was conducted using the Taiwan National Health Insurance Research Database. Each patient was individually tracked from 1999 to 2009 to identify the diagnosis of JIA and uveitis using the International Classification of Diseases diagnostic codes. Multivariate logistic regression was used to determine the risk factors and complications of uveitis in patients with JIA.ResultsThe study cohort had 2636 cases of JIA and included juvenile rheumatoid arthritis (57.7%), enthesitis-related arthritis (ERA) (39.2%), and psoriatic arthritis (3.1%). The average annual incidence of JIA and JIA-associated uveitis were 4.93 (range, 3.93–6.23) and 0.25 (range, 0.12–0.37) cases per 100,000 population, respectively. The average period prevalence of JIA was 33.8 cases per 100,000 population. Uveitis occurred in 4.7% of patients with JIA, while JIA-associated uveitis was complicated by cataract (11.2%) and glaucoma (24.8%). Enthesitis-related arthritis was significantly associated with uveitis (OR: 3.47; 95% CI: 2.24–5.37) (p<0.0001). Uveitis diagnosed before JIA was the most significant risk factor for complications of glaucoma or cataract (OR: 3.54; 95% CI: 1.44–8.72) (p = 0.006).ConclusionsThe incidence of JIA is low but that of JIA-associated uveitis is increasing. Higher percentage of males in patients with ERA and the strong association between ERA and uveitis are unique for children with JIA in Taiwan. Uveitis diagnosed before arthritis is an important risk factor for complications. Continuous ophthalmologic follow-up is needed for children with JIA or uveitis of unknown etiology.
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