Sleep deprivation and the skin

Abstract

Sleep is an under-evaluated symptom when assessing patients with cutaneous disease. Consequently, the relationship between sleep deprivation and disease burden is often not considered. The focus of our review article is to explore the bidirectional relationship between sleep and cutaneous disease investigating the disruption in circadian rhythmicity and skin homeostasis. Management strategies should focus on optimizing disease control coupled with improving sleep hygiene.

Introduction

Sleep is defined as a temporary suspension of awareness with decreased sensitivity to external stimuli and it is regulated by the circadian rhythm.¹ Sleep is vital in calibrating skin physiology: skin surface pH, transepidermal water loss (TEWL), blood flow and skin temperature. Various hormones and proinflammatory cytokines exhibit circadian rhythmicity. The hypothalamus sits at the centre of the endocrine system and produces hormones via several axes: growth hormone levels increase during sleep; cortisol decreases in the evening and peaks in the early morning, and melatonin peaks during the night and decreases in the early hours of the morning.² Proinflammatory cytokines such as interleukin (IL)-1, IL-2, IL-6, tumour necrosis factor (TNF)-α are increased at night and promote sleep whereas anti-inflammatory cytokines such as IL-4 and IL-10 are elevated after awakening and inhibit sleep.² Sleep deprivation can disrupt the release of hormones and inflammatory markers exacerbating skin integrity and thus worsening skin diseases.³

There are a number of proposed hypotheses for explaining the mechanism of sleep disturbance. The driving force underlying sleep disturbance in patients with dermatological conditions is nocturnal symptoms, including pruritus and pain. Inflammation and sleep are related through central and peripheral circadian mechanisms that regulate cortisol and melatonin levels, cytokines as well as core physiological properties of the skin such as pH, water loss and permeability.^3–5 Circadian disruption of hormones such as melatonin and cortisol promotes itch and therefore exacerbates disease flares. Similarly, increased TEWL at night, decreased sebum production, histamine release and variation in pruritogenic inflammatory cytokines can worsen nocturnal symptoms.^6,7

We explore the complex bidirectional relationship between sleep deprivation and cutaneous disease.

Atopic dermatitis

Sleep disturbance is a common symptom of atopic dermatitis (AD), affecting approximately 60% of children with AD.⁸ Multiple studies utilizing actigraphy and polysomnography have reported increased frequency of night-time awakenings, greater difficulty falling asleep and decreased sleep efficiency in individuals with AD.⁹

Current guidelines for managing sleep disturbance in patients with AD focus on disease control with sleep disturbance as a measure of control.¹⁰ However, Chang and Chiang recommend a dual approach to optimize treatment for AD with the use of intensive topical therapies coupled with sleep-directed therapies such as improving sleep hygiene and antihistamines to reduce pruritus.¹¹ Sleep hygiene strategies include regular sleep and wake times, relaxing bedtime routines, quiet sleeping environment and limiting caffeine intake.¹¹

Skin ageing

Ageing is a progressive process determined by both intrinsic and extrinsic factors that synergistically lead to a loss of structural integrity and physiological function.¹² Intrinsic (chronological) ageing results from physiological changes over time, at a predetermined genetic rate. Extrinsic factors are potentially modifiable and include sun exposure, pollution, diet and sleep deprivation.¹³

In a 2015 study, 60 healthy women were categorized as either poor-quality (regularly slept 5 h per night) or good-quality (regularly slept 8 h per night) sleepers and their skin health was evaluated using the SCore for INtrinsic and EXtrinsic skin Aging (SCINEXA) score – a validated metric that accounts for both intrinsic and extrinsic factors of skin ageing.¹⁴ Participants who were good sleepers were reported to have significantly lower SCINEXA scores, 30% reduced TEWL and significant improvement in skin reddening post ultraviolet exposure, relative to people who were poor sleepers. The patients who were classified as good sleepers also felt more attractive and were happier with their appearance.

Subsequently, Jang et al. showed a significant reduction in skin hydration after 1 day of sleep deprivation and a significant reduction in skin elasticity.¹⁵

Psoriasis

In a cross-sectional, case–control design,¹⁶ 179 participants with psoriasis were compared with 105 controls utilizing several validated indices measuring psoriasis severity, sleep quality, insomnia severity and itch severity. The results were striking showing 25% of patients with psoriasis report clinical insomnia compared with 10.5% of controls. Over half of patients with psoriasis were classified as poor-quality sleepers compared with 22% of controls. Itch (pruritus) emerged as the most consistent statistical predictor of sleep deprivation; a later systematic review suggested treatments targeting pruritus were successful in mitigating sleep deprivation.³ An observational study suggested patients with obstructive sleep apnoea (OSA) had almost double the risk of developing psoriasis than the general population, hypothesizing an upregulation of inflammation precipitating disease onset.¹⁷

In a study of 152 patients with psoriasis commencing adalimumab, participants had impaired sleep at baseline and the authors found a 15% improvement in sleep quality following 16 weeks of adalimumab treatment, which may reflect reduced systemic inflammation or direct improvement of sleep.¹⁸ Duan and Silverberg formulated a detailed framework illustrating factors mediating the bidirectional relationship between chronic inflammatory skin diseases and sleep impairment that can be used to inform management, which includes, but is not limited to, targeted treatment such as wet wrap therapy and emollients for decreased skin barrier function, cognitive behavioural therapy and antidepressants to address psychosocial factors, and antihistamines and systemic therapy to break the itch–scratch cycle and modulate inflammatory pathways.¹⁹

Acne

In one study (n = 40), subjectively worse sleep quality was associated with objectively worse acne²⁰; of note, although questionnaire-based measures were used, objective measures of sleep quality such as polysomnography were not.

Rosacea

A case–control study enrolled 608 patients with rosacea and 608 healthy controls with sleep quality measured using the Pittsburgh Sleep Quality Index (PSQI).²¹ They found that 52.3% of patients with rosacea experienced poor sleep quality compared with 24.0% of controls, with the patients scoring higher on the PSQI. Moreover, various inflammatory markers (matrix metallopeptidase-9, Toll-like receptor-2, cyclic adenosine monophosphate) were raised in patients who were sleep deprived suggesting poor sleep may aggravate rosacea through local skin inflammation. A recent retrospective study found patients with OSA had a higher risk of developing rosacea because of greater sympathetic activation and the release of catecholamines that can affect facial skin vasculature and therefore trigger rosacea.²²

Pemphigus

Pemphigus vulgaris is an autoimmune bullous dermatosis disease characterized by often painful blisters and erosions. Night pain can disrupt sleep onset and cause night and early morning wakening,²³ which in turn can cause greater sensitivity to pain.²⁴ Pedroni et al. speculate that chronic pain caused by skin erosions could be the driving force for sleep deprivation.²⁵ An additional contributing factor to sleep loss is the use of glucocorticoid therapy to treat pemphigus with Gillin et al. showing in their study that higher doses of glucocorticoids reduce total rapid eye movement sleep time.²⁶

Hidradenitis suppurativa

A higher incidence of OSA has been reported in patients with hidradenitis suppurativa (HS) compared with controls indicating HS as a potential risk factor for OSA.²⁷ Moreover, both HS and OSA are associated with increased levels of TNF-α²⁸ and inadequate symptom management has been shown to contribute to poor sleep quality with Kaaz et al. reporting pain and pruritus as common causes of sleep disruption in patients with HS.²⁹

Miscellaneous

In a placebo-controlled trial, significant improvement in sleep in patients with chronic spontaneous urticaria treated with desloratadine was reported³⁰; however, sleep also improved, by a lesser degree, in the placebo group. Sleep deprivation has been reported in other inflammatory skin diseases such as prurigo nodularis³¹ and vitiligo.³²

Conclusions

Although often not evaluated, sleep is an essential factor to consider when managing dermatological diseases. A dynamic interplay of elements creates a bidirectional relationship between sleep deprivation and skin diseases including, disruption of circadian rhythmicity, altered skin homeostasis, symptoms (including itch and pain) and comorbidities such as OSA. Management strategies should focus on optimizing disease control coupled with improving sleep hygiene.

Learning points

• Pruritus is a central symptom in inflammatory dermatoses and is strongly associated with sleep deprivation.

• Optimizing disease control and reducing disease burden can in turn improve sleep quality.

• Inflammatory skin diseases increase the likelihood of developing sleep disorders such as insomnia and obstructive sleep apnoea.

• Sleep deprivation and cutaneous diseases can have a bidirectional relationship whereby an increase in disease severity can cause sleep loss and poor sleep can worsen disease burden.

Funding sources

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Data availability

No new data were generated or analysed in support of this research.

Ethics statement

Ethical approval: not applicable. Informed consent: not applicable.

CPD questions

Learning objective

To gain up-to-date knowledge of the various mechanisms involved in the relationship between sleep deprivation and skin disease.

Question 1

Which class of medication is associated with sleep loss in pemphigus?

• (a)

  Beta-blockers.

• (b)

  Antihyperlipidaemics.

• (c)

  Glucocorticoids.

• (d)

  Mineralocorticoids.

• (e)

  Alpha-blockers.

Question 2

Based on the literature, which of the following sleep disorders almost doubles the risk of developing psoriasis?

• (a)

  Obstructive sleep apnoea (OSA).

• (b)

  Bruxism.

• (c)

  Narcolepsy.

• (d)

  Rapid eye movement (REM) disorder.

• (e)

  Hypersomnolence disorder.

Question 3

Which of the following biologics is shown to improve sleep quality in psoriasis?

• (a)

  Rituximab.

• (b)

  Trastuzumab.

• (c)

  Cetuximab.

• (d)

  Adalimumab.

• (e)

  Infliximab.

Question 4

Which of the following inflammatory markers is found to be increased in hidradenitis suppurativa (HS) and OSA?

• (a)

  Matrix metallopeptidase (MMP)-9.

• (b)

  Erythrocyte sedimentation rate (ESR).

• (c)

  Transforming growth factor (TGF)-β.

• (d)

  Procalcitonin.

• (e)

  Tumour necrosis factor (TNF)-α.

Question 5

Which of the following cytokines are elevated after wakening and inhibit sleep?

• (a)

  Interleukin (IL)-1.

• (b)

  IL-2.

• (c)

  IL-4.

• (d)

  IL-6.

• (e)

  TNF-α.

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Author notes

Conflicts of interest The authors declare no conflicts of interest.