Complementary Therapies in Medicine 35 (2017) 85–91

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Complementary Therapies in Medicine

journal homepage: www.elsevier.com/locate/ctim

A new topical treatment of atopic dermatitis in pediatric patients based on MARK

Ficus carica L. (Fig): A randomized, placebo-controlled clinical trial☆
Shirin Abbasia, Mohammad Kamalinejadb, Delara Babaiec, SeyedMohammad Shamsd,
⁎ ⁎
Zahra Sadre, Mehdi Gheysarif, Vahid Reza Askarig,h, , Hassan Rakhshandehg,
a
Department of Persian Medicine, School of Persian and Complementary Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
b
School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
c
Department of Allergy and clinical immunology, Mofid Children’s hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
d
Department of Biomedical Engineering, Faculty of Engineering, South Tehran Branch, Islamic Azad University, Tehran, Iran
e
Firouz Abadi Hospital, Iran University of Medical Sciences, Tehran, Iran
f
Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
g
Pharmacological Research Center of Medicinal Plants, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
h
Department of Pharmacology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

A R T I C L E I N F O A B S T R A C T

Keywords: Background: Atopic dermatitis (AD) is a common, chronic, relapsing and inflammatory skin disease character-
Atopic dermatitis ized by pruritus and xerosis (dry skin). Its prevalence is on the increase worldwide, particularly in children. As
Ficus carica L. the pathogenesis of AD involves a complex interaction of genetic, environmental and immunological factors, its
Hydrocortisone 1.0% definitive treatment is difficult.
Herbal agents
Objective: This clinical trial was designed as equivalence study to investigate the effect of aqueous extract of
Scoring atopic dermatitis (SCORAD)
edible dried fig fruit on the severity of AD as measured with scoring atopic dermatitis (SCORAD), in comparison
with Hydrocortisone 1.0% as the routine treatment of AD and base cream as a placebo.
Method: Forty five children aged 4 months to 14 years with mild to moderate AD (SCORAD < 50) were ran-
domly assigned, in a double blind manner, to three treatment groups in order to perform a randomised, double
blinded, placebo-controlled clinical trial. The patients were instructed to apply their allocated creams twice a
day for two weeks.
Results: The randomised, placebo-controlled trial indicates that the new treatment had significantly increased
efficacy in terms of reducing the SCORAD index, pruritus and intensity scores in comparison with
Hydrocortisone 1.0% (p < 0.05) and the placebo failed to ameliorate the symptoms.
Conclusion: Safety, efficacy, tolerability, and symptom relief were considerable in fig fruit extract in comparison
with hydrocortisone 1.0%. This clinical trial suggests that fig fruit extract can be used instead of low potent
corticosteroid in mild to moderate cases of AD.

1. Introduction Hanifin-Rajka criteria are widely used as a standard diagnostic of AD

Atopic dermatitis (AD) or atopic eczema is an inflammatory, chronic
and relapsing skin disease, which is characterized by severe pruritus
and xerosis (dry skin).1–3 Its prevalence has increased worldwide, Fif-
teen to twenty percent (15–20%) of children and 2–10% of adults are
affected by this disease.4–8 Atopic disorders such as asthma, allergic
rhinitis and atopic eczema develop from the interaction of genetic and
environmental factors.9–11 In addition to this, the immune system is
considered as another dimension of pathogenesis. However, the
and are frequently used as inclusion criteria in clinical trials. The se-
verity scoring of AD is extremely important for research purposes and
clinical practices.12–16
The chronic and relapsing nature of atopic dermatitis, different le-
vels of severity, and age limitations of chemical medications, led to the
search for safer and more appropriate therapeutic agents.
Complementary and alternative medicines (CAM) are non-allopathic
systems of medicine. These methods are including meditation, herbal
remedies and homeopathy which are growing in popularity globally

☆
This study was approved by the Ethics Committee of Mashhad University of Medical Sciences (N#930235/1/281) and was registered at the Iranian Registry of Clinical Trials
(N#IRCT2014101419529N1). The parents of all patients gave written informed consent.
⁎
Corresponding authors.
E-mail addresses: askariv941@mums.ac.ir (V.R. Askari), rakhshandehh@mums.ac.ir (H. Rakhshandeh).

http://dx.doi.org/10.1016/j.ctim.2017.10.003
Received 26 May 2017; Received in revised form 27 August 2017; Accepted 9 October 2017
Available online 13 October 2017
0965-2299/ © 2017 Elsevier Ltd. All rights reserved.
S. Abbasi et al.
and several clinical studies on the efficacy of these complementary
methods are ongoing. Iran, Greek and China have long history of using
these methods, especially for chronic diseases like eczema.17–21 Avi-
cenna and Galen,22 two prominent ancient scientists had described
eczema as an inflammation process in the skin. They also stated that,
for prevention of eczema development, the skin should be strengthened
so that it does not receive any irritant material. Additionally, they
prescribed some herbal medicines such as Chamomile, Marigold, and
Marshmallow, among others for the treatment of eczema.23–28
Effective constituents of these plants such as flavonoid, palmitic
acid, saponins and linoleic acid have been investigated in several stu-
dies. These compounds have proven effectiveness in eczema. However,
their utilization is limited due to lack of availability in most parts of the
world, complex processing, high cost, and side effects for some of them
as well as inadequate evidences for their usage in place of standard
treatments.29–31
In this study, the effect of aqueous extract of dried fruit of Ficus
carica L. as a new topical treatment for mild to moderate atopic der-
matitis in children was investigated. Fig fruit, (Arabic, al-Tin; Persian,
Anjeer) is one of the herbal plants, which had been used as topical agent
for skin inflammation or skin edema by prominent and famous scientist.
The current research is based on the phytochemical of herbs and Iranian
Traditional Medicine references. It is one of the first plants to be cul-
tivated by humans and its origin is the Middle East or Western Asia but
today it is distributed throughout the world.32,33 Previous studies have
demonstrated that fig extract (leaves and fruits) is rich in phenols,
flavonoids and with anti-oxidant, anti-inflammatory, antiviral and an-
tibacterial properties, which aid us in atopic dermatitis treatment.29,34
In addition, F. carica contains a high number of amino acids and is rich
in zinc, calcium, magnesium and copper which are effective in wound
healing.29,35
2. Materials and methods
2.1. Extraction and cream preparation
Estahban edible fig (F. carica cv. green) was purchased from local
markets of Estahban County, Fars Province, Iran, in September 2014.
Medicinal plants specialist confirmed these materials taxonomically. A
voucher specimen (N = 8072) has been deposited at the Herbal
Medicine Formulation Research Group at the Faculty of Pharmacy
Shahid Beheshti University of Medical Sciences (Tehran, Iran). 100 g of
fig samples were washed and then macerated in 200 ml of water at
25 °C for 1 h. Then they were boiled in water for 10 min. Thereafter,
when they were cooled to room temperature, they were squeezed and
filtered through a filter in order to eliminate un‐dissolved material and
finally they were concentrated in a bain-marie at 50 °C for 48 h until a
honey-like consistency was obtained. 40 g extract was extracted from
100 g fig (8% concentration). Creams were prepared in the same
package with specific number, which was determined by a statistician
only.36–39 Melfi cream contained aqueous extract of Ficus carica L. sun-
dried fruit and base cream. The components of commercially available
base cream (Farabi base cream) were cetostearyl alcohol, petroleum
jelly, glycerin, mineral oil, preservative, and anti-oxidant. In a pilot
study, an aqueous extract of fig fruit having different concentrations
were prepared (4, 6 and 8%). A dose response effect was noticed and
8% concentration was chosen for our further experiments. Hydro-
cortisone 1.0% and base cream were supplied by Emad Pharmaceutical
Co. (Iran, Tehran) and Farabi Pharmaceutical Co. (Iran, Isfahan), re-
spectively.
2.2. Total phenolic contents (TPC) of the extract
TPC of extract was defined using Folin–Ciocalteu (FC) reagent
which described previously40,41 with minor modification as followed.
In brief, aliquot (100 μl) of the extract (20 μg/mL) was mixed equal
86
Complementary Therapies in Medicine 35 (2017) 85–91
volume of water in test tube. 200 μl of FC reagent were added to the
tube, and after 2 min, 2600 μl of a 5% (w/v) sodium carbonate solution
added. The mixture was incubated at 40 °C for 20 min with shaking.
The tubes were then quickly be cool, allowed to the developing color
and read at 760 nm using a UV–vis spectrophotometer (Shimadzu,
Tokyo, Japan). Estimation of phenolic compounds was done using
polyphenol reference calibration curve of Gallic acid (GA) in range of
0.5–10 mg/L41 The amount of TPC was expressed as mg of GA
equivalent (GAE) per gram of dry extract. Blank was prepared with
100 μl of distilled water instead of extract.
2.3. Participants
The current study is a double-blinded, randomized, and placebo-
controlled type and was conducted from November 2014 to December
2015 in Asthma and Allergy Clinic, Mofid Children’s Hospital (Tehran,
Iran). Subjects that participated in the study were infants and children
of up to 15 years with mild to moderate AD diagnosed according to the
Hanifin-Rajka criteria.
• Inclusion criteria
a. Child must be under 15 years of age
b. Child has been diagnosed with AD according to the Hanifin-Rajka
criteria
c. Children have been diagnosed with mild to moderate AD
(SCORAD < 50) 42,43
• Exclusion criteria
a. Child has severe AD (SCORAD > 50)
b. Child has a secondary skin infection
c. Child has another skin disease
d. Child has immunodeficiency disorder
e. Child has used TCS or TCI within the previous 2 weeks
f. Child has used systemic corticosteroids or immunosuppressive
agents within the previous 4 weeks
2.4. Study design
2.4.1. Sample size
The sample size was determined based on the results of the pilot
study conducted in Hadhrat Zahra Educational Hospital, Qum, Iran,
afterwards it was validated by using results from all the participants
included in the study. A pilot study was done on 7 patients with mild to
moderate atopic dermatitis to determine the standard deviation of this
measure to inform a sample size calculation for the main study. Patients
were randomly assigned to intervention (fig fruit extract cream) and
control groups (base cream). They received treatment for two weeks.
SCORAD was measured before and after treatment. According to the
pilot study, the difference between mean effect of fig fruit extract cream
(Melfi cream) treatment and control group was 13.5, and standard
deviation of the all treatment effects was 12.5, in terms of SCORAD
index. A sample size of ≈ 14 participants at 80% power and 5% sig-
nificance level for each group was calculated.
2.4.2. Randomization and blinding
Participants were shared into three groups via block randomization
with a block size of three and 20 blocks were designed. The patients
were randomly assigned (in a 1:1:1 allocation ratio) to three treatment
groups; aqueous extract of F. carica (n = 20), topical hydrocortisone
1.0% (n = 20), and placebo (n = 19). Creams were packed in 30 g of
same sterile plastic containers with a specific number. In this study,
both the investigator and patients were blinded as regards the assign-
ment of the study drugs.
S. Abbasi et al.
2.4.3. Treatment regimen and diagnosis
The duration of this study was 14 days. Children were randomized
to receive topical F. carica cream 8% (Melfi cream), hydrocortisone
1.0% or placebo (base cream). Each child randomly received one of the
three products with the specified dose of tip finger unit (TFU) for his or
her age on the skin lesions, twice daily for 2 weeks. Subjects were under
the additive-free diets, including: preservatives, colorings, flavor sub-
stances, among others.36–39
The diagnosis of AD on inclusion was assessed using the
Hanifin–Rajka criteria, and the AD severity was graded according to the
severity SCORAD system. The SCORAD index, as the most widely used,
well-validated instrument and empirically reliable scale that measures
the severity of AD, was evaluated by allergist in allergy clinic in pe-
diatric hospital. SCORAD included objective signs (A: extent, B: in-
tensity) and subjective symptoms (C): A = The extent score based on
body surface area using the ‘rule of 9′, B = The intensity score based on
six clinical signs in atopic dermatitis, namely: edema, erythema, oozing
or crusting, excoriation, lichenification and dryness graded in the range
of 0–3 (0: none, 1: mild, 2: moderate and 3: severe), C = The score for
subject symptoms includes pruritus and sleep disturbance; Visual ana-
logue scale is between 0 and 10 38,42–44. With this three values (A, B and
C), total SCORAD is calculated by using followed formula;
A B
+7× +C
5 2
SCORAD < 25: mild,
SCORAD = 25–50: moderate,
and SCORAD > 50: severe.38,42–44
In this study, our participants had mild to moderate SCORAD.
SCORAD was investigated at first visit, and after two weeks of treat-
ments for follow-up.
2.5. Statistical analysis
Among 121 atopic dermatitis patients who visited the Allergic Clinic
in Mofid Hospital, only 59 met the inclusion criteria and agreed to
participate in the study. Among these 59 patients, 14 were omitted from
the study as a result of incomplete medical records and not being able
to contact them. Finally, analyses were carried out for 45 children in
three groups. As the normal distribution assumption was violated, the
non-parametric Wilcoxon rank-sum test was chosen with regards to the
within group comparisons, whereas analysis of covariance (ANCOVA)
was used for the comparison of final scores between treatment groups
after adjustment for the initial scores. Statistical analyses were per-
formed using the Statistical Package of Social Sciences (SPSS) (ver. 24)
and a P-value of less than 0.05 was considered to be statistically sig-
nificant.
3. Results
3.1. Determination of TPC
Generally, FC reagent is often utilized to evaluation of TPC in nat-
ural products. The value of TPC for the extract was 6.5 mg GAE/g dried
extract.
3.2. Baseline characteristic
Fig. 1 shows the disposition of the patients and the flow of parti-
cipants through the study. Totaly, 45 children 22 (48.8%) boys and 23
(51.1%) girls were enrolled and completed the study. The mean age of
the patients in Melfi cream, hydrocortisone 1.0% cream and placebo
groups were 38, 28 and 27 months, respectively. At the onset of the
study, all the patients had mild to moderate SCORAD values (< 50).
Table 1 shows the demographic information of the three treatment
groups. As shown in the Table, no significant differences were observed
87
Complementary Therapies in Medicine 35 (2017) 85–91
between any of the treatment groups means in terms of age, SCORAD,
pruritus, and intensity scores. And based on a Chi-square analysis, a
significant difference in gender was found between the treatment
groups (P = 0.001).
3.3. Efficacy outcomes
The severity of AD as evaluated by the SCORAD index and the se-
verity of the main symptoms (intensity and pruritus) before and after
treatment are summarized in Table 2. The results show that Melfi cream
and hydrocortisone 1.0% cream effectively reduced the SCORAD index
and severity of symptoms (intensity and pruritus) (p < 0.001) and the
placebo cream failed to ameliorate the symptoms. The results of AN-
COVA showed that there is significant difference among the three
groups in SCORAD index F (2, 41) = 52.620, p < 0.001.
The results of pairwise comparison of estimated marginal means in
SCORAD index showed that there is a significant difference between the
estimated marginal means of Melfi cream and hydrocortisone 1.0%
cream groups (p = 0.046). Moreover, the pairwise comparison results
showed that the Melfi cream provided significantly better outcomes in
comparison with the base cream (p < 0.001). As shown in the results,
there is a significant difference between estimated marginal means in
pruritic score of Melfi cream and hydrocortisone 1.0% cream groups
(p = 0.004). But there is no significant difference between estimated
marginal means in intensity score of Melfi and hydrocortisone 1.0%
groups (p = 0.399). Table 3 shows pairwise comparison of estimated
marginal means in SCORAD, pruritus and intensity).
Moreover, Fig. 2 depicts digital images of the face of a pediatric
patient with AD taken before and after two-week treatment by Melfi
cream. Fig. 2A shows face images before the topical treatment and
Fig. 2B shows the same face after two-week treatment by Melfi cream.
3.4. Second phase of follow-up and safety
Patients were followed-up for two weeks after discontinuation of
treatment. Given the fact that 15 of the 45 patients were not available
for the second phase of follow up, this part of the study was not re-
ported completely. The summary of the second phase is as follows: In
Melfi cream group, 11 children were cured completely, SCORAD de-
creased in 3 children and increased in 1 child. One child was not
available. In the hydrocortisone 1.0% group, 8 children were cured
completely, SCORAD decreased in 1 child and increased in another one.
Four children were not available. In the placebo group 1 child was
cured completely and SCORAD increased in 4 children. Ten children
were not available. In this study, no side effects such as urticaria,
flushing, erythema, pruritus or irritant contact dermatitis were ob-
served in any of the patients during the treatment and follow-up period.
4. Discussion
To the best of our knowledge, this study was the first investigating a
new alternative topical treatment of atopic dermatitis in children pa-
tients based on an herbal extract, fig fruit extract. Nowadays, the uti-
lization of herbal medicine has immensely become popular all over the
world. This is particularly important in infants and children because of
the severe side effects of some chemical therapeutic agents. TCSs as the
principal treatment for AD, have several topical and systemic adverse
effects such as skin atrophy, adrenal axis suppression or even growth
retardation especially in infants and little children. These side effects
are increased by epidermal barrier dysfunction which is a fundamental
pathogenesis of AD 45–48. Although topical calcineurin inhibitors (TCIs)
as a new generation of anti-inflammatories does not have these side
effects, the prohibition of its usage for children under 2 years, ne-
phrotoxicity or the increasing risk of skin cancer, which were reported
in some researches, resulted in concerns about their safety, especially
during infancy.49–51
S. Abbasi et al. Complementary Therapies in Medicine 35 (2017) 85–91

Fig. 1. Flow of participants through the study.

Fig. fruit is one of the oldest human foods which has a very high
safety profile.52 Fig (F. carica L.) is a subtropical, dioeciously fruit tree,
which is an important member of the genus of several species in the
Moraceae family.53 This fruit is an important source of minerals such as
calcium, zinc, magnesium, etc., which can be used in wound healing
and skin repair. High amounts of flavonoids have been detected in
various parts of F. carica such as fruit, leaf or latex. Use of leaves and
latex of F. carica for contact dermatitis have been reported in many
literatures; fruit is the safest part of the plant.54,55 Flavonoids, subgroup
of phenolic compounds, and anthocyanins have anti-oxidant, anti-in-
flammatory and anti-microbial activities.29,56–58 These activities are
very important for the prevention and treatment of atopic dermatitis.
It is interesting to note that dried figs have higher phenolic content
than fresh fruits. Different amount of phenolic compounds were re-
ported in different figs varieties.29 In our experiment, we evaluated the
total phenolic compound of the aqueous extract which is 6.5 mg GAE/g
of dried extract. The yellowish fruit skin color of F. carica cv. Sabz
(native to Iran) has medium level of phenolic compounds as compared
to the black species. However, being native is important because of easy
availability.59 The seeds are rich in lectin with immunomodulatory
properties. Also, the sterols content of fig may also strengthen im-
munity and inhibit inflammation process.52,60–62 In addition to the
above reasons, colonization with Staphylococcus aureus is an important
complexity in atopic dermatitis and some studies have shown that the
extract of Ficus carica L. has antibacterial activity against Staphylococcus
aureus, Bacillus subtilis, Proteus vulgaris, Pseudomonas aeruginosa, and
Escherichia coli.23,63
Its availability all over the world, rapid processing, and also its fair
price, makes it an eligible choice. For example, in Iran the price of
hydrocortisone cream is be three times more higher than that of fig fruit

Table 1
Comparison of the baseline characteristics between three groups.

Characteristic Melfi cream N = 16 hydrocortisone 1% cream N = 14 Placebo (base cream) N = 15 All N = 45 P value

Boy 4 (25.5%) 5 (35.7%) 13 (86.6%) 22 (48.8%) < 0.01*

Girl 12 (72.5%) 9 (64.2%) 2 (13.3%) 23 (51.1%)
Age (Mean ± SD) 38.0 ± 44.1 28.36 ± 37.25 27 ± 27 31.33 ± 36.47 0.667
SCORAD (Mean ± SD) 33.84 ± 10.05 29.53 ± 13.58 28.48 ± 10.34 30.61 ± 11.3 0.386
Intensity (Mean ± SD) 6.75 ± 2.81 6.28 ± 2.84 5.6 ± 2.22 6.22 ± 2.62 0.484
Pruritus (Mean ± SD) 5.31 ± 2.70 3.5 ± 2.76 5.0 ± 2.80 4.64 ± 2.8 0.177

* P < 0.05.

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S. Abbasi et al. Complementary Therapies in Medicine 35 (2017) 85–91

Table 2
SCORAD, intensity and pruritic scores before and after treatment for all groups.

Before treatment (baseline) After treatment P value

Mean ± SD Mean ± SD

SCORAD Fig fruit extract 8% (Melfi cream) 33.84 ± 10.05 14.85 ± 8.83 < 0.0001
hydrocortisone 1.0% cream 29.53 ± 13.58 16.73 ± 9.44 < 0.001
base cream 28.48 ± 10.34 34.30 ± 12.61 Treatment faileda

Intensity Fig fruit extract 8% (Melfi cream) 6.75 ± 2.81 3.06 ± 1.80 < 0.0001
hydrocortisone 1.0% cream 6.28 ± 2.84 3.28 ± 1.77 < 0.001
base cream 5.60 ± 2.22 6.93 ± 2.89 Treatment faileda

Pruritus Fig fruit extract 8% (Melfi cream) 5.31 ± 2.70 1.93 ± 1.91 < 0.001
hydrocortisone 1.0% cream 3.50 ± 2.76 2.35 ± 1.98 < 0.004
base cream 5.0 ± 2.80 5.66 ± 2.92 Treatment faileda

a
This result indicates that the treatment failed to reduce symptoms.

extract cream.
The results of the present randomized, placebo-controlled clinical
trial showed that the new treatment based on aqueous extract of edible
fig fruit is an effective alternative topical treatment of atopic dermatitis
for pediatric patients. The results showed that the new treatment sig-
nificantly reduced the severity of symptoms and signs in terms of
SCORAD, pruritus and intensity scores. The SCORAD, pruritus and in-
tensity scores in both Melfi and hydrocortisone 1.0% groups were sig-
nificantly lower than that in the baseline, while the base cream failed in
them.
Despite the complication and time consumption during routine
clinical use, scoring atopic dermatitis (SCORAD) is the most frequently
used scoring system for measuring the severity of atopic dermatitis for
clinical and research purposes. The original SCORAD index was de-
veloped as a composite scoring index in 1993 by European Task Force
on Atopic Dermatitis.42,43 The SCORAD index is composed of two
parts:1 objective signs: extent and intensity of lesions and2 Subjective
symptoms: pruritus and sleep disturbance.
In comparison with the standard treatment (hydrocortisone 1.0%
cream) using the Melfi cream based on aqueous extract of edible fig
fruit significantly increased the effectiveness of the treatment in terms
of decreasing the SCORAD index and pruritus scores. In addition, no
significant difference was observed between both treatments as regards
the reduction of intensity scores and they had almost equal effect.
5. Study limitations
Limitation of this study was the preservation of cream and severity
of atopic dermatitis. Melfi cream had no preservatives and therefore
parents stored it in the refrigerator. Another problem is connected with
children who returned to special clinic of allergy in hospital. Most of
them had severe atopic dermatitis and were not included in the study;
however mothers prefer to use herbal treatment instead of chemical
therapy.
For double blindness, the placebo, hydrocortisone 1.0% and Melfi
creams were packed in the same containers. Since the patients (and
their parents) did not know the exact color and appearance of these
creams, having different color and appearance may not affect the
blindness. However, this non-identicalness besides the non-contribution
of patients, the small sample size and the short duration of the study can
be mentioned as limitations of this study.
6. Conclusion
In summary, the data reveal that the application of aqueous extract
of fig fruit (Ficus carica L.) can offer better treatment outcome than
Hydrocortisone 1.0% in mild to moderate atopic dermatitis in pediatric
patients. Nevertheless, clarification of the role, effectiveness and lim-
itations of this herbal agent in AD treatment may require further stu-
dies.
Conflict of interest
The authors declare that they have no conflict of interest.
Author’s contribution
Abbasi, Kamalinejad and Rakhshandeh designed and conducted the
study. Abbasi, Babaie, Sadr and Gheysari acquired the data. Shams
analyzed the data. Abbasi, Shams, Rakhshandeh and Askari wrote the
manuscript. Abbasi, Shams, Rakhshandeh and Askari revised the
manuscript. Kamalinejad and Rakhshandeh provided technical support.
Askari also performed final critical review of this study.

Table 3
ANCOVA pairwise comparison for three treatment groups.

Treatment (I) Treatment (II) Mean Difference (I-II) Std. Error 95% confidence Interval for difference Sig.a

Lower Bound Upper Bound

SCORAD Melfi cream base cream −23.284 b

2.384 −28.100 −18.468 < 0.001
Melfi cream hydrocortisone 1.0% cream −4.959b 2.410 −9.826 −0.092 0.046
hydrocortisone 1.0% cream base cream −18.325b 2.418 −23.209 −13.442 < 0.001

Pruritus Melfi cream base cream −3.940b 0.505 −4.960 −2.919 < 0.001
Melfi cream hydrocortisone 1.0% cream −1.640b 0.533 −2.717 −0.564 0.004
hydrocortisone 1.0% cream base cream −2.299b 0.535 −3.379 −1.219 < 0.001

intensity Melfi cream base cream −4.552b 0.582 −5.727 −3.376 < 0.001
Melfi cream hydrocortisone 1.0% cream −0.498 0.584 −1.678 0.682 0.399
hydrocortisone 1.0% cream base cream −4.054b 0.595 −5.255 −2.852 < 0.001

a
Adjustment for multiple comparisons: Bonferroni.
b
The mean difference is significant at the 0.05 level.

89
S. Abbasi et al.
Fig. 2. The face of a patient with AD before (A) and after treatment by Melfi cream (B).
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