ORIGINAL ARTICLE

Sleep disturbance in children with

moderate/severe atopic dermatitis:
A case-control study
Anna B. Fishbein, MD, MS,a Kelly Mueller,b Lacey Kruse, MD,c Peter Boor, MD,c
Stephen Sheldon, MD,d Phyllis Zee, MD, PhD,e and Amy S. Paller, MS, MDb
Chicago, Illinois

Background: Sleep is disturbed in 60% of children with atopic dermatitis (AD).

Objective: To characterize sleep in a cohort of children with moderate-to-severe AD and determine

methods for assessment of sleep disturbance.

Methods: A case-control study compared children age 6 to 17 years who have moderate-to-severe AD with
age- and sex-matched healthy controls. Participants wore actigraphy watches and completed sleep- and
disease-specific questionnaires.

Results: Nineteen patients with AD and 19 controls completed the study. The patients with AD
experienced wake after sleep onset (WASO) for 103 plus or minus 55 minutes as compared with 50 plus
or minus 27 minutes in the controls (P \ .01). They had a higher frequency of restless sleep, daytime
sleepiness, difficulty falling back to sleep at night, and teacher-reported daytime sleepiness. Disease
severity correlated well with WASO (total SCORing Atopic Dermatitis score: r = 0.61, P \ .01; objective
SCORing Atopic Dermatitis score: r = 0.58, P = .01; and Eczema Area and Severity Index: r = 0.68, P \.01).
The Children’s Dermatology Life Quality Index sleep question correlated with WASO (r = 0.52, P = .03), but
self-reported itch severity did not (r = 0.28, P = .30).

Limitations: The study cohort was small.

Conclusion: Children with moderate-to-severe AD experience more WASO and lower sleep efficiency than
healthy controls but similar bedtime and wake time, sleep duration, and sleep onset latency. ( J Am Acad
Dermatol http://dx.doi.org/10.1016/j.jaad.2017.08.043.)

Key Words: actigraphy; atopic dermatitis; circadian; itch; nocturnal; scratch; screening; sleep; sleep
disturbance; wake after sleep onset.

clinical disease remission.4 This causes significant

A topic dermatitis (AD) affects 10% to 20%

of children in the United States.1 Sleep
disturbance is reported in approximately
60% of children with AD2-6 and can persist despite
morbidity, including neurocognitive effects, decreased
linear growth, and overall poor quality of life for
the children and their families.2,7 Although sleep

From the Divisions of Allergy & Immunology,a Dermatology,c and
Pulmonology,d Ann & Robert H. Lurie Children’s Hospital; the
Department of Dermatology,b Northwestern University Fein-
berg School of Medicine; and the Center for Circadian and
Sleep Medicine,e Northwestern University.
Supported by the American College of Allergy, Asthma and
Immunology Young Faculty Support Award (to AF) and by
the Ann and Robert H. Lurie Children’s Hospital of Chicago (to
AF) and the Society for Pediatric Dermatology William Weston
Grant (to LK and AP). This project was supported by grant
K12HS023011 (to AF) from the Agency for Healthcare Research
and Quality. The content is solely the responsibility of the
authors and does not necessarily represent the official views of
the Agency for Healthcare Research and Quality.
Conflicts of interest: None declared.
Accepted for publication August 25, 2017.
Reprints not available from the authors.
Correspondence to: Anna B. Fishbein, MD, MS, Ann and Robert H.
Lurie Children’s Hospital of Chicago, Northwestern University,
Department of Allergy & Immunology, 225 E Chicago Avenue,
#60, Chicago, IL 60611. E-mail: afishbein@luriechildrens.org.
Published online October 28, 2017.
0190-9622/$36.00
Ó 2017 by the American Academy of Dermatology, Inc.
http://dx.doi.org/10.1016/j.jaad.2017.08.043

1
2 Fishbein et al J AM ACAD DERMATOL
n 2017

disturbance is one of the most bothersome AD Disease severity

symptoms, families report that it is inadequately Disease severity was determined in the clinic by
addressed at clinical appointments.2,8 Guidelines list using SCORAD score (with a moderate score being
sleep as a key aspect of disease control,9,10 yet little is [25 and a severe score being $51).16,18 SCORAD
known about the objective characteristics or optimal score incorporates AD skin signs with total body
methods of assessing sleep in AD.11 surface area affected (objective SCORAD). Subjective
Children with AD have frequent overnight findings (sleep interference and itch severity)18 are
12
movements, presumably related to itch. This results added to create a total
in increased wake after sleep SCORAD score. Secondary
onset (WASO) and poorer CAPSULE SUMMARY measure included the
sleep efficiency.13 Actigraphy Eczema Area and Severity
Sleep disturbance is inadequately
Index (EASI).19
d
is a validated measure of
sleep/wake in AD in the assessed in atopic dermatitis (AD).
outpatient setting.14 A recent d Compared with controls, children with Actigraphy and sleep
study using actigraphy found moderate-to-severe AD have diaries to measure sleep
that children with AD of any approximately 50 minutes more of wake disturbance
severity had approximately after sleep onset. Sleep was objectively as-
20 minutes more WASO than d Children with disturbed sleep despite sessed by using actigraphy
controls.15 Other studies have aggressive management of their AD may (accelerometry) with event
focused on adults or included benefit from referral to a sleep medicine markers and patient- or
few children. specialist. parent-written daily sleep
Characterization of the diaries. Actigraphy is a non-
burden of sleep disturbance invasive, accurate method to
using patient and/or parent assess sleep disturbance in the home environment,11
report and objective measure is needed. Our objec- and it correlates with polysomnography when
tives were (1) to characterize sleep using both measuring sleep quality and scratching in
consistently scored actigraphy and parent- and/or AD.14,20,21 Actigraphy was measured using the
patient-reported measures in a cohort of children with Actiwatch Spectrum device (Philips Respironics,
moderate-to-severe AD and (2) to determine methods Bend, OR). The Actiwatch resembles a wristwatch
to assess for sleep disturbance in this population. and is worn on the nondominant wrist. With
movement, the watch generates an output voltage
METHODS via the piezoelectric effect on dielectric crystals. The
Study procedures and participants resultant information is stored in the watch in
This case-control study was conducted with 30-second epochs as an activity count. Data were
patients (6 to 17 years old) and their parents in the analyzed with Philips Actiware 6 software (Philips
allergy, dermatology, or general pediatrics clinics. Respironics). Bedtime and wake time are set by the
Patients with a moderate-to-severe SCORing Atopic scorer. The software applies a validated algorithm to
Dermatitis (SCORAD) score higher than 2516 interpreting activity counts as sleep versus wake.22
diagnosed by an allergist or dermatologist according Established parameters from the pediatric sleep
to Hanifin and Rajka criteria17 were eligible for literature, a medium wake threshold value of activity
enrollment if the parents answered yes to the screening counts, and immobile minutes of 3 minutes for sleep
question ‘‘Does your child have problems sleeping onset and 5 minutes for sleep offset were chosen.23
related to eczema?’’ Subjects with AD were compared The sleep parameters measured by actigraphy
with age- and sex- matched and race/ethnicity-similar included bedtime, sleep start time, sleep end time,
healthy controls with no history of AD. Institutional wake time, time in bed, sleep duration, sleep onset
review board approval was obtained by the Ann & latency, wake after sleep onset, fragmentation index,
Robert H. Lurie Children’s Hospital of Chicago. and sleep efficiency. Actigraphy was scored similarly
For inclusion, comorbid conditions were required to validated methods by a trained scorer blinded to
to be well controlled. Children with asthma were disease severity.23
required to have an asthma control test score higher
than 19, and children with allergic rhinitis (AR) Patient- and parent-reported measures of
were required to have a parent or patient report sleep, itch, and quality of life
confirming the absence of sleep interference. The parent or caregiver of the participant
Patients were asked not to take oral antihistamines completed the Pediatric Sleep Questionnaire
during the study. All other therapies were continued. (PSQ).24 Patients completed itch Visual Analogue
J AM ACAD DERMATOL
VOLUME jj, NUMBER j
Abbreviations used:
AD: atopic dermatitis
AR: allergic rhinitis
CDLQI: Children’s Dermatology Life Quality
Index
EASI: Eczema Area and Severity Index
PSQ: Pediatric Sleep Questionnaire
SCORAD: SCORing Atopic Dermatitis
WASO: wake after sleep onset
Scale and Numeric Rating Scale. Patients older than
7 years, with parent input, answered SCORAD
questions about sleep and itch and the Children’s
Dermatology Life Quality Index (CDLQI).25
Statistical analysis
Demographics and descriptive data were
compared by using the chi-square test, t test for
normally distributed data, or Wilcoxon signed rank
test for non-normal data. The Spearman correlation
coefficient was used for correlations. Statistical
analysis was performed with SPSS software (version
23.0, IBM Inc, Armonk, NY). A P value less than .05
was considered significant.
RESULTS
Demographic data and disease severity
Patient characteristics are presented in Table I. In
all, 20 patients with AD and 20 controls with no
history of AD were recruited. Actigraphy sleep
measurements were completed in 19 patients with
AD and 19 controls. Subjects with AD and controls
had actigraphy scored on the basis of a similar
number of days (6.4 6 1.0 vs 6.4 6 1.1 [P = .87]).
Of the 19 patients with AD, 11 reported taking an oral
antihistamine before enrollment; this was stopped
during all nights of the study period in only 4 of 11
patients.
General sleep characteristics as defined by
actigraphy
Table II describes actigraphy-measured sleep
characteristics in patients with AD versus the control.
The most significant sleep parameters affected by AD
were WASO and sleep efficiency. The control WASO
data were similar to previously published data.26
WASO difference was most notable on weekdays
in patients with AD versus in the controls
(101.5 6 54.3 min vs 51.9 6 31.7 [P \.01]). Time in
bed on weekdays was similar for patients with AD
and the controls (529.4 6 76.7 vs 522.1 6 66.7 min
[P = .75]). On weekends, subjects with AD had longer
sleep duration than the controls (555.6 6 77.9 vs
496.4 6 81.8 minutes [P \.03]).
Fishbein et al 3
AD patients with AR did not have increased WASO
compared with patients without AR (106.2 6 63.3 vs
97.4 6 37.3 min [P = .76]). Positive screening for
sleep-disordered breathing did not increase WASO
( = 130.1 6 78.3 vs 90.8 6 33.4 min [P = .18]), and
disease severity was similar (SCORAD,
 = 60.5 6 20.5 vs 56.9 6 25.3 [P = .76]).
Parent-reported sleep characteristics
The parental responses to the PSQ demonstrated
differences between the patients with AD (n = 19)
and the control subjects (n = 17), with significantly
more responses of yes regarding restless sleep (9 vs 2
[P = .01]) daytime sleepiness (8 vs 0 [P \ .01]), and
difficulty falling back to sleep at night after waking
(7 vs 1 [P = .02]) being given by parents of the
patients with AD. Although not statistically signifi-
cant, 3 of 19 parents of children with AD noted
comments from a supervisor or teacher indicating
that their child was sleepy during the day, compared
with 0 parents of controls.
Correlation of patient- and parent-reported
sleep characteristics with actigraphy
PSQ-reported bedtime, but not wake time,
correlated with actigraphy during the week
(r = 0.57, P = .02 [n = 17]) or weekend (r = 0.56,
P = .03 [n = 16]). However, length of time to fall
asleep was parent-reported to be 33.3 6 28.1 minutes
and did not correlate with the lower number
found via actigraphy measure (r = -0.08, P = .76
[n = 16]).
Although the sleeplessness score within SCORAD
did not predict WASO (r = 0.37, P = .12), total
SCORAD score correlated with WASO (r = 0.61,
P \ .01). WASO also correlated with objective
SCORAD score (r = 0.58, P = .01) and EASI
(r = 0.68, P \ .01). Itch did not correlate with
WASO (r = 0.28 and P = .30 for the Visual Analogue
Scale and r = 0.20 and P = .42 for the Numeric Rating
Scale). Adding the CDLQI sleep question to EASI
numerically correlated better with WASO (r = 0.95,
P \.01) than did EASI alone (r = 0.68, P \.01).
DISCUSSION
Children in our cohort had worse sleep than
previously reported in AD. Although wake time
and bedtime were similar to those in the controls,
the patients with AD had an average of almost 1 hour
less sleep per night. This could be explained by
greater severity of AD in of our population, with
increased night-time movements.26
As in other studies, there was no prolongation in
sleep onset latency compared with in the
controls.14,27 The likely explanation is that patients
4 Fishbein et al J AM ACAD DERMATOL
n 2017

Table I. Characteristics of the study population (n = 40)

Characteristic Atopic dermatitis (n = 20) Controls (n = 20) P value
Age (y), mean (SD) 11.0 (3.2) 11.5 (3.3) .68
Age range 5.9-6.1 6.2-16.6
Male sex (%) 13 (65) 13 (65)
Race/ethnicity
African American (%) 5 (25) 4 (20) .98
Asian (%) 4 (20) 3 (15)
Latino (%) 4 (20) 5 (25)
White (%) 6 (30) 7 (35)
Other (%) 1 (5) 1 (5)
Comorbidities
Asthma (%) 12 (60) 1 (5) \.01
Allergic rhinitis (%) 14 (70) 3 (15) \.01
Food allergies (%) 12 (60) 0 (0) .01
Sleep-disordered breathing (%)*y 7 (35) 1 (5) \.01
Periodic limb movement syndrome (%)*y 0 (0) 0 (0)
Atopic dermatitis severity
Moderate (%) 8 (40) d
Severe (%) 12 (60) d
Total SCORing Atopic Dermatitis score, mean (SD) 58 (21) d
Range 28-92 d
Objective SCORing Atopic Dermatitis score, mean (SD) 47 (17) d
Range 23-79 d
Eczema Area and Severity Index, mean (SD) 24 (15) d
Range 4-57 d
Itch, mean (SD)
Visual Analog Scale 5.4 (2.5) d
Numeric Rating Scale 6.0 (2.8) d
Atopic dermatitis age of onset (mo), mean (SD) 11.1 (21.1) d
Range 0-96 d
Taking a systemic immunosuppressant (%) 2 (10) d

SD, Standard deviation.

*Determined from the Pediatric Sleep Questionnaire Screening Criteria.
y
Based on a sample size of 35.

Table II. Sleep characteristics overall

Characteristics Atopic dermatitis (n = 19) Control (n = 19) P value
Bedtime (HH:MM), mean (SD) 22:36 (1:15) 23:26 (1:37) .08
Wake time (HH:MM), mean (SD) 07:40 (0:37) 8:08 (1:21) .18
Sleep start time (HH:MM), mean (SD) 22:49 (1:13) 23:42 (1:47) .09
Sleep end time (HH:MM), mean (SD) 07:34 (0:38) 8:00 (1:22) .21
Time in bed (min), mean (SD) 544.5 (73.0) 522.3 (53.5) .29
Sleep duration (min), mean (SD) 524.3 (72.1) 498.3 (61.6) .24
Sleep onset latency (min), mean (SD) 13.7 (14.8) 15.7 (22.3) .74
Wake after sleep onset (min), mean (SD) 103.4 (55.4) 49.8 (26.6) <.01
Fragmentation Index, mean (SD)* 26.4 (19.2) 18.9 (6.9) .12
Sleep efficiency, %, mean (SD)y 76.8 (12.7) 85.9 (4.9) <.01

Boldface indicates statistical significance. HH:MM indicates that time is specified in hours and minutes.
SD, Standard deviation.
*This is an index value that includes mobility and short sleep bouts. Sum of the percentage of mobile and percentage of 1-minute immobile
bouts divided by the number of immobile bouts for the given interval. Definition adapted from Phillips Respironics software
(Philips Respironics, Bend, OR).
y
The percentage of time spent in bed sleeping.
J AM ACAD DERMATOL
VOLUME jj, NUMBER j
with moderate-to-severe AD, in contrast to those
with milder disease,15 have chronic sleep
deprivation secondary to difficulty in maintaining
sleep.28,29 This results in a large sleep drive (natural
tiredness at night), and the patients fall asleep easily
despite their pruritus. Patients with AD, as compared
with controls, had longer sleep duration on
weekends, suggesting compensation for weekday
sleep deprivation.
Self-reported itch did not correlate with sleep
disturbance, perhaps because the study was
underpowered to see this association. It remains
possible that scratching drives sleep disturbance.
Bender at al found that scratching overnight did not
correlate with AD patientereported itch scores,20
possibly because of decreased awareness of
nocturnal itch and inaccurate reporting of
night-time pruritus. Other mechanisms driving
scratch could be nocturnal worsening of skin barrier
function,30 circadian rhythms of T-cellemediated
inflammation,11 and/or overall increased skin
sensitivity to allergens overnight.31
In addition, we postulate that children with AD
develop overactive sensory input secondary to
damaged skin.11 This could explain why some
children have persistent sleep disturbance despite
control of their skin disease. Afferent neurons are
primed to be hyper-responsive to stimuli on the skin
(blankets, night-time sweating, and clothing of
any type, but particularly certain textiles such as
wool).
In clinical assessment of sleep disturbance,
disease severity should be noted as having the
strongest correlation with WASO. The CDLQI sleep
question was a fair estimate of WASO. Clinicians
might address the patient or parent perception of
restless sleep, daytime sleepiness, and difficulty
falling back to sleep at night. However, the parent
report of sleep habits might be inaccurate,
and objective assessment via actigraphy or
polysomnography should be considered.
Strengths of our study include its
well-characterized, racially/ethnically diverse
patient population. The study design with age- and
sex-matched controls allowed for adequate
interpretation of sleep parameters, given their
variance by age. The major limitation of this study
was the small cohort of patients. We did not
perform polysomnography with electroencephalo-
graphy to characterize sleep stages and cannot
completely rule out sleep disordered breathing as a
cause for some sleep disturbance. Actigraphy can
overestimate WASO in children and adolescents
compared with polysomnography, which was
Fishbein et al 5
reported in 1 study as being overestimated by
10 minutes on average.32
Research is ongoing to standardize assessment
measures of sleep disturbance in AD so that sleep
itself can be targeted as a domain for treatment.
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