Evaluation of Melatonin Supplementation in Children with Atopic Dermatitis at Aboreesh Hospital, Egypt

Journal of Environmental Treatment Techniques

2020, Volume 8, Issue 3, Pages: 1084-1088

J. Environ. Treat. Tech.

ISSN: 2309-1185

Journal web link: http://www.jett.dormaj.com

Evaluation of Melatonin Supplementation in

Children with Atopic Dermatitis at Aboreesh

Hospital, Egypt

Doaa M. Ali , Marwa M. Saeed , Walaa Ibrahim and Amany S. Elsayed *

MD, Professor of Dermatology, Dermatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt

MD, Assistant professor of Family Medicine, Family Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt

MD, Lecturer of Medical Biochemistry& Molecular biology, Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo

University, 11562 Cairo, Eygpt

MSc, Family Medicine specialist, Mitghmer health district, Dakahlia governate, Egyptian Ministry of Health, Egypt

Received: 25/03/2020

Accepted: 29/06/2020

Published: 20/09/2020

Abstract

Atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin disease commonly associated with poor sleep efficiency. Lower

nocturnal melatonin secretion was significantly associated with sleep disturbance in the children with AD, which is a major factor

leading to an impaired quality of life (QOL). Evaluation of melatonin role in management of AD associated with sleep disorders to

improve quality of life (QOL). Randomized clinical trial used double blind placebo pre and post experimental for intervention group

with 43 children in each group who were recruited from dermatology outpatient clinic Aboreesh Hospital. This study included children

with AD aged from (5-15) years and involving at least five % of total body surface area. Patients were randomly allocated into

Melatonin group and Placebo group. Full history was taken and full general and dermatological examination using scoring atopic

dermatitis index were done. Serum melatonin and IgE levels were assessed before and after melatonin supplementation. There was

significant difference between pre and post regarding serum Melatonin and IgE except in blood level of melatonin in placebo group.

As regard serum level of melatonin become 14pg/ml while before study was 59 pg /ml. But at placebo group started 25.5pg/ml and

become 17pg/ml. IgE showed significant difference in pre and post study, as it was 132 before melatonin and become 24 after

supplementation of melatonin while in placebo group drop from 129 to 27. There was significant improvement in total eczema score in

post study markedly from 69 to two in Melatonin group and from 72 to three in Placebo group. Melatonin supplementation is a safe

and effective way to improve the sleep-onset latency and disease severity in children with AD.

Keywords: Atopic dermatitis, Melatonin, SCORAD, QOL, IgE, Family practice

Introduction¹

including everyday activities and sleep, and psychosocial

wellbeing. There is not necessarily a direct relationship

between the severity of the atopic eczema and the impact of

the atopic eczema on quality of life [5].

Atopic eczema (atopic dermatitis (AD)) is a chronic

inflammatory itchy skin condition that develops in early

childhood in the majority of cases. It is typically an episodic

disease of exacerbation (may occur as frequently as two or

three per month) and remissions and in some cases it maybe

continuous [1]. Health promotion has been defined as “the

process of enabling people to increase control over their

health and it determinants, and there by improve their health”.

One of the most important determinants of quality of life

Melatonin is the main product secreted by the pineal gland

during the night it has a great functional versatility including

the regulation of circadian and seasonal immune responses by

regulation of the T helper 1& 2 (TH1& 2) balance and

cytokine production. Effects of melatonin in different

autoimmune diseases aren’t clear [6]. Melatonin deficiency

and increase serum IgE play a significant role in the sleep

disturbance [7]. AD also called in Clinical Medicine atopic

eczema is an increasing common childhood multi-factorial

and chronic inflammatory skin disease [8]. The immune-

pathological basis of AD is complex, butit is known that it is

mediated by a TH1/TH2 biphasic inflammatory response that

involves several cytokines, such as IL-4 IL-5, IL-13 and IFN-

y. Regarding to melatonin and atopic dermatitis a first report

shown evidences of a dysfunction of the melatonin secretion

in patients with atopic eczema, possibly due to a partially

reduced activity of the sympathetic nervous system, which is

involved in the control of melatonin secretion, it was shown

an elevation of salivary melatonin in patients with AD. By

contrary, in the phases of disease outbreaks it has been

documented a reduction in the serum levels of both melatonin

and B-endorphin. It has been reported that melatonin

(

QOL) is coetaneous body image of patient, so skin diseases

are one of the most important factors which influences on it

2]. 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

[3]. Eczema is known to adversely affect daytime behavior. It

is unclear whether this is a direct effect or mediated by the

effect of eczema on sleep quality [4]. Healthcare professionals

should adopt a holistic approach when assessing a child’s

atopic eczema at each consultation, taking into account the

severity of the atopic eczema and the child’s quality of life,

Corresponding author: Amany S. Elsayed, MSc, Family

Medicine specialist, Mitghmer health district, Dakahlia

governate, Egyptian Ministry of Health, Egypt. E-mail:

amany_salaheldin@hotmail.com.

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Journal of Environmental Treatment Techniques

2020, Volume 8, Issue 3, Pages: 1084-1088

suppresses the development of at dermatitis-like skin lesions.

It has been shown that melatonin related to the inflammatory

response associated with contact hypersensitivity and that

one time per night), difficulty falling asleep after waking up at

night, or difficulty waking up in the morning. (b) Compliant:

main symptom that necessitates the medical advice. (c)

Present history: Onset, course, duration of AD, lesions,

pattern of spread, symptoms and sleep pattern. (d) Past

History: development, nutrition, vaccination, disease,

operations, drugs and exposure to allergen and dietary recall.

(e) Family History: consanguinity, allergic diseases (skin

allergy -Bronchial asthma).

melatonin

treatment

attenuated

the

delayed-type

hypersensitivity (DTH) [6]. The use of melatonin is supported

by National institute for Health and Care Excellence (NICE)

in their Clinical Guideline on the diagnosis and management

of chronic fatigue syndrome in children. Within that

Guideline it stated that melatonin may considered for children

and young people who have sleep disorder [9].

.7 Clinical Examination

Full general and dermatological examination was done

using SCORAD scale which is a useful tool for assessing AD

widely used, the Sleep Disturbance Scale for Children

Materials and Methods

.1 Study design

This study is randomized clinical trial used double blind

(

SDSC) and QOL questionnaire, this questionnaire aims to

placebo pre and post experimental for intervention group.

This study was carried out through a period of nine months

from the 1st of March 2017 to the end of October 2017.

measure how much skin problem have affect child daily life.

Scoring system in this study includes Eczema Score Consists

of three sub score, Extent: After give each affected body part

its own weighted score summation done, Intensity: give score

from 0-3) according to degree of intensity then summation,

Subjective: estimated by patient for sleep loss and irritability

from 0-10) then summation Final score by (extent /5) +

(7xintensity)/2) +subjective If <25 mild 25-50 moderate >50

sever. Quality Scoring system: After summation of each item

from 0-3) and total score we considered >60% impacted

Sleep scoring system: After summation of each item (from 1-

.2. Ethical approval

(

Official permissions were obtained from the family

medicine department, pediatric department, the director of the

outpatient clinic and the scientific ethical committee of the

collage. An informed consent was obtained from every patient

before filling the questionnaires. They were reassured about

the strict confidentiality of any obtained information, and that

the study results would be used only for the purpose of

research.

(

) and total score we considered >60% impacted.

.8 Laboratory investigations

.3 Participants

Eighty-six children were included in this study. Children

Five-milliliter peripheral venous blood samples were

withdrawn at 9 A.M. from placebo group and melatonin group

subjects, then blood was allowed to clot and then centrifuged

at 8000×g for 5 min to separate the serum which was stored at

were recruited from dermatology outpatient clinic Aboreesh

Hospital, Faculty of Medicine, Cairo University in the period

nine from the 1st of March 2017 to the end of October 2017.

All included children had AD, skin changes above five % of

body surface area and sleep insufficiency subjective

complaint. Children with systemic illness, blood disease,

hormonal disorders, congenital anomalies and children

documented sleep disorders or neuro-psychiatric-disorders

were excluded from the study.

−

80 °C until used for estimation of: (a) melatonin level in all

subjects before and after supplementation by ELISA and (b)

total serum IgE level in all subjects

supplementation.

before and after

.8 Statistical analysis

Results were expressed as mean ± standard deviation (SD)

for normally distributed data (Total SCORAD, Quality of life

score and Sleep disorders score) and median interquartile

range (IQR) for not normally distributed data (Serum

Melatonin and IgE). Comparison of different variables

between groups was performed using unpaired t test in

normally distributed data (Total SCORAD, Quality of life

score and Sleep disorders score) or Mann Whitney U test in

not normally distributed data (Serum Melatonin and IgE).

Pair-wise comparison (pre- versus post-assessment) within the

same group for different variables was performed using paired

t test in normally distributed data (Total SCORAD, Quality of

life score and Sleep disorders score) or Wilcoxon Sign

Rank test in not normally distributed data (Serum Melatonin

and IgE). Statistical Package for Social Sciences (SPSS)

computer program (version 20 windows) was used for data

analysis. P value ≤ 0.05 was considered significant and < 0.01

was considered highly significant.

.4 Sample size& sampling

As effect size of treated agents' melatonin (18.6%) with

confidence level 95% and power 80%. sample was 43

children in each group of total 86 children. Patients were

randomly allocated into Melatonin group and Placebo group.

.5 Intervention& data collection

Melatonin three mg/day or placebo were administrated by

subjects one hour before bed time for four weeks. Placebo

was manufactured by the same drug company manufacturing

melatonin. Dosage was once daily for four weeks. Patient

arranged by electronic coding each patient in each group

represented by number. Melatonin and placebo were arranged

by a pharmacist coding all the container by specific number

and letter coding only was known by him. At the end of the

result he translates the coding. There was no drop out. All the

children patients were submitted to the following after

parental approval:

Results

.6 A structured interviewing questionnaire

a) Personal history: name, age, sex, residence. Level of

The present study included 86 subjects that were divided

(

into two groups: placebo group (n=43) and melatonin group

(n = 43). Age of patients ranged from 5 to 15 with a mean of

5.23 and 5.46 years respectively, Placebo group included 18

(41.9%) males and 25 (58.1%) females and the melatonin

group included 24 (55.8%) males and 19 (144.2%) females.

There were no significant differences between the placebo

group and melatonin group regarding age and sex (P = 0.12, P

consciousness, appearance (color) and vital signs subjective

symptoms of sleep disturbances children and parents (main

care giver) completed pediatric sleep evaluation questionnaire

to evaluate subjective symptoms of sleep disturbances the

questions included problems with sleep initiation. (Taking 30

minutes to fall asleep) or maintenance (waking up for at least

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Journal of Environmental Treatment Techniques

2020, Volume 8, Issue 3, Pages: 1084-1088

0.19) respectively (Table 1). The Total SCORAD, Quality

of life score, Sleep disorders score, Serum Melatonin and

IgE showed a highly significant reduction (P = 0.001) within

both groups, while it showed non-significant differences

between both groups post- Supplementation (P >0.05).

Comparing both groups pre- Supplementation revealed a

statistically highly significant increase in Serum Melatonin (P

human patients with AD were so limited studies from 2012 up

tell now. The present study aimed to evaluate role of

melatonin in treatment of AD associated with sleep disorders

in children between (5-15) years. At the same time the present

study showed impaction of atopic eczema on QOL and sleep

disorders by using quality score and sleep disorder score.

Distribution among the two groups was 44.2% female in

Melatonin group while male percentage was 55.8%. However

female in Placebo group was 58.1% and male percentage was

0.001) in favor of the Melatonin group (Table 2).

1.9%. There was no significant difference in age distribution

Discussion

between both groups with mean age 5.5 years. Age group in

the current study was chosen (5-15) as age of school entry

child can take tablet at bed time, and can be examined easy.

That was limited to human adult (>18 years of age) [11].

Similarly, the study conducted in Taiwan for the same

purpose, the age group was (1-18) year. However, the study

conducted in France chose age group of (7-14) year in

evaluation of role of melatonin in AD in children [12].

Regarding laboratory results serum melatonin was 58.8±

Numerous epidemiologic and clinical studies within the

past decade have demonstrated that genetic, environmental,

and immunological factors all affect AD development as well

as its clinical picture, degree of severity, and course in

addition to the classic predictors of AD development such as

family history and urban environment. Recently recognized

predictors of disease course and severity include onset of AD

signs and symptoms before 12 months of age and the presence

of FLG gene mutations and concomitant IgE sensitization

early in life. The environment continues to be a topic of great

interest in the quest to better understand the pathologic

pathways in AD [10].

7.5pg/ml in Melatonin group and 25.5± 17.8 in Placebo

group; significantly higher in Melatonin group. While serum

IgE was 129.5± 43.2& 132.8± 47.5 in Placebo& Melatonin

groups respectively with no significant difference between

both groups. As regard the mean extent of eczema score in pre

supplementation of the drug, there was no significant

difference between two groups with mean extent score 59.3±

Main Outcomes and Measures: The primary

outcome was AD severity evaluated using SCORAD index,

with scores ranging from (0-103) and greater scores indicating

worse symptoms. Secondary outcomes included sleep

variables measured by SDSC subjective change in sleep and

dermatitis, sleep variables, serum melatonin and IgE levels.

Clinical trials investigated the supplement of melatonin in

2.0 & 54.5± 29.2 in Placebo& Melatonin groups

respectively.

Table 1: Age and sex distribution between both groups

Placebo group (n = 43)

Melatonin group (n = 43)

p- value

0.12

Age (Mean +SD)

Sex distribution N (%)

Male

5.2321

5.4647

18 (41.9%)

25 (58.1%)

24 (55.8%)

19 (44.2%)

.19

Female

p-value: level of significance

Table 2: Descriptive and inferential statistics for all dependent variables at different measuring periods at both groups

Placebo group (n = Melatonin group

P value*

(n = 43)

Total SCORAD

Pre-Supplementation

Post-Supplementation

P value**

71.95 ± 11.98

3.42± 5.79

0.001

68.77± 22.27

2.22 ± 5.21

0.001

0.413

0.238

Quality of life score

Sleep disorders score

Serum Melatonin

Pre-Supplementation

Post-Supplementation

P value**

18.34 ± 9.74

1.60± 1.95

0.001

16.72± 7.25

1.48 ± 4.46

0.001

0.079

0.914

Pre-Supplementation

Post-Supplementation

P value**

55.51 ± 21.67

27.25± 3.02

53.06± 18.74

29.3 ± 14.24

0.413

0.075

0.001

Pre-Supplementation

Post-Supplementation

P value**

25.5 (17.89)

17.69 (18.8)

58.84 ( 57.58)

14.3 (4.72)

0.001

0.254

0.001

IgE

Pre-Supplementation

Post-Supplementation

P value**

129.5 (43.21

27.21 (19.21)

0.001

132.84± 47.52

24.32 (18.2)

0.001

0.08

0.58

Inter-group comparison; ** intra-group comparison of the results pre- and post-Supplementation.

P > 0.05 = non-significant, HS P < 0.01 = highly significant, P = Probability.

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2020, Volume 8, Issue 3, Pages: 1084-1088

AD impacts sleep by different ways; Itching, Irritability

and disturbed circadian rhythm and also it impacts QOL with

different results in variable studies [13]. Sleep disturbance has

also been reported to have a major influence on the QOL of

AD patients and there was significant correlation between

sleep quality and QOL in children. Thus, the use of QOL

indices, AD patients and care-givers have the potential to

experience greater satisfaction with treatment [14].

The total eczema score in both Placebo& Melatonin

groups was 71.9± 119& 68.7± 22.2 respectively with no

significant difference. As regard sleep pattern in both groups

by using SDSC, results were similar scores with no significant

difference as Melatonin group was 53.0± 18.7 and Placebo

group was 55.5± 17.6. The QOL in both groups was affected

estimated by quality score that calculated using QOL

questionnaire that were 16.7± 7.2 in Melatonin group and

21.4 min after melatonin treatment compared with after

placebo; P = 0.02) and disease severity by SCORAD

(SCORAD decreased by 9.1 compared with after placebo;

P<0.001) [7]. On the other hand, there was no significant

difference between quality and sleep score in post study in

Placebo and Melatonin group.

Implications for research and/or practice:

Further studies are required to explore the mechanisms of

action of melatonin and clinical implications, could serve as a

useful evaluating tool in management of AD. It is important

that clinicians evaluate the severity of AD and ask general

questions about itching, sleep, impact on daily activities, and

persistence of disease during each patient visit and follow-up

with the complaint of sleep disturbance. Family physician

should screen for sleep disorders with AD. Management of

sleep disturbance in AD should focus on adequate disease

control of AD as well as possible medical interventions to

help improve sleep. The pathophysiology of sleep disturbance

in AD is extremely complex, and further research is needed to

better understand the interplay of the immune system,

circadian rhythm, and environmental factors implicated in

both AD and sleep. AD has been found to be associated with

impaired QOL. While some patients and families are better

able to cope than others. So health education about triggers

factors and protective mechanisms is indicated in cases of

atopic dermatitis in primary care.

8.3± 9.7 in Placebo group with no significant difference

between two groups pre intervention. These findings were

agreed with the results reported by Ca’mfferman et al., who

found that sleep not impacted significantly while disturbed

sleep is reported in 47%–60% of patients and is a major factor

leading to an impaired quality of life [4].

Post intervention analysis demonstrated that serum level

of melatonin became 14.3± 4.7pg/ml in Melatonin group but

at placebo group became 17.6± 18.8pg/ml. Melatonin level

started high at the morning nine AM in children who have

AD. After supplementation of melatonin three mg before bed

time serum level of melatonin significantly decreased it seems

that external melatonin alters circadian rhythm. As standard

treatment of eczema was resumed, also course of eczema was

remission and exacerbation. IgE decreases spontaneously, the

present study IgE showed significant difference in pre and

post study with mean 24 after supplementation of melatonin

Conclusion

Melatonin supplementation is a safe and effective way to

improve the sleep-onset latency and disease severity in

children with AD. But study conducted was limited so further

studies are needed.

4.3± 18.2 in Melatonin group while in Placebo drop to 27.2±

9.2. Of course significant improvement but with no

Acknowledgment

Great thanks to the two studied groups who helped us to

perform my work.

difference between Placebo and Melatonin that indicates that

melatonin gives no difference of statistically value. While

other data conducted in 2014 suggested that melatonin inhibits

development of atopic eczema and reduces total serum IgE

[15]. Equally important that was significant improvement in

Ethical issue

total eczema score in post study markedly from (69 to 2) in

Melatonin group and Placebo from (72 to 3) in P group. This

indicates that melatonin have a role but limited or unclear.

Together with total sleep score drop from (53 to 29) in

Melatonin group and from (55.5 to 27) in Placebo group.

Then quality score improved from (17 to 1) and from (18 to 2)

in Melatonin and Placebo groups respectively.

Authors are aware of, and comply with, best practice in

publication ethics specifically with regard to authorship

(avoidance of guest authorship), dual submission,

manipulation of figures, competing interests and compliance

with policies on research ethics. Authors adhere to publication

requirements that submitted work is original and has not been

published elsewhere in any language.

Both group scores improved but other study showed that

melatonin has significant influence as the following; in France

a study conducted showed melatonin supplement for short

period at bed time give dramatic response by decreasing

ASOL (awaking sleep onset latency). Also in that study

analyzed plasma melatonin concentration before and after

supplementation, results showed plasma melatonin

concentrations were significantly higher with a recovery in the

circadian rhythm and actual sleep time was significantly

longer with substantial reduction in sleep onset, latency and

night awakenings [12]. Furthermore, sleep score significantly

improved in study conducted in China using three mg

melatonin daily at bed time for four weeks [16]. Also, in

agreement with study evaluated the QOL in 101 AD patients

compared with healthy controls and showed that patients with

AD had reduced DLQI scores compared to controls (p＜

Competing interests

Authors declare there is no conflict of interest regarding

the publication of paper.

Authors’ contribution

All authors of this study have a complete contribution for

data collection, data analyses and manuscript writing.

Funding

No source of funding.

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