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Thursday, November 5, 2015

Nocturnal eczema: Review of sleep and circadian rhythms in children with atopic dermatitis and future research directions

Atopic dermatitis (AD) is characterized by intense nocturnal pruritis, which can severely impact sleep continuity and quality. Sixty percent of children with AD experience sleep disturbance due to their condition, with 83% reporting disturbance during exacerbations. Sleep deprivation has been shown to alter immune function. In the case of school-aged children, it can impair linear growth, and in fact short stature has been described in children with AD only when associated with insufficient sleep. Fishbein et al review our current understanding of the role of sleep and circadian rhythms in nocturnal AD, current treatments, and future research directions (J Allergy Clin Immunol 2015; 136: 1170-1177).

Despite the widespread prevalence of sleep dysfunction in children with AD, the mechanisms that lead to it are not well understood. Nighttime factors such as cortisol nadir, increased skin temperature, and poor barrier function may contribute to noctural AD exacerbations, as may circadian variation in the expression of inflammatory cytokines such as IL-2, IL-6, and the pruritus-specific TH2 cytokine IL-31. In addition, children with AD can have comorbidities including increased susceptibility to infection; heightened sensitivity to sensory stimulation; and restless leg syndrome, defined as an urge at night and prior to sleep to move the legs.

Treatment of pediatric AD should focus on disease control with sleep disturbance as an important measure. Topical steroids can improve sleep disturbance, as can wet wrap therapy. Antihistamines are often first line therapy but there is limited data to support this practice and future research is necessary. Actigraphy has been demonstrated to provide an accurate assessment of sleep in children, and standardized scoring parameters do not currently exist. Children with AD need a standardized, patient-centered outcome tool that could assess their sleep impairment, correlated with objective sleep measures. Given that approximately 10% of genes are under circadian control, future exploration of circadian biomarkers would open possibilities for a novel treatment paradigm as well.

1 comment:

  1. The association between atopic dermatitis (AD) and restless leg syndrome (RLS) mentioned in the article warrants additional discussion. The authors cited an article which found 40% of AD patients also met criteria for RLS as defined by the IRLSSG diagnostic criteria. The authors then suggested the diagnosis of RLS may have been "secondary to itch-induced movements". It is important to distinguish between movement of the legs due to itching from AD and movement due to RLS. Current IRLSSG diagnostic criteria for RLS include the following: urge to move the legs due to an uncomfortable sensation; symptoms are worse with inactivity or when lying down; symptoms improve or resolve with movement such as walking; symptoms are worse at night; most importantly, symptoms are not solely accounted for by another medical condition. The pathophysiology of RLS is not well understood, but it has been proposed that derangements in iron stores, the dopaminergic system, or the thalamus may explain RLS. Current recommendations for treatment of RLS include dopamine agonists and gabapentin. Interestingly, it has been suggested that antihistamines, especially sedating antihistamines, can actually precipitate or worsen RLS.

    If we believe that our patients with AD have RLS then we should seriously consider stopping antihistamine therapy and adding therapy directed at treating RLS such as dopamine agonists or gabapentin. If, however, we believe limb movement is secondary to itching from uncontrolled AD and not RLS we should work to control the AD and not confuse the picture by adding an additional diagnosis that could result in additional, extraneous therapy.

    It is helpful to be reminded of the consequences of inadequate sleep caused by uncontrolled AD. I appreciate the thoughts regarding the use of melatonin, light therapy, chronotherapy and other phramacotherapy as possible treatment options for patients struggling with disrupted sleep as a result of their uncontrolled AD. Thank you for this helpful review.