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Understanding the
Role of Emollients
in Atopic Dermatitis
Management
IFC
Understanding the
Role of Emollients
in Atopic Dermatitis
Management
Adelaide Ann Hebert
David Luk Chi Kang
Hardyanto Soebono
Hugo Van Bever
Inne Arline Diana
Kyu-Han Kim
Maria Victoria Dizon
Marysia Stella Recto
Yoke Chin Giam
Zakiudin Munasir
CONTENTS
Foreword 3
Introduction 4
What to consider when selecting moisturizers
Classification of moisturizers
Anti-inflammatory agents
10
11
12
14
17
18
19
SMART goals
20
Conclusions 21
References 23
FOREWORD
Effective treatment of atopic dermatitis (AD) involves treating the skin
barrier defect inherent in these patients. To do this, patients should be
advised to have adequate hydration and to use moisturizers regularly.
There are but a few available moisturizers supported by scientific evidence.
The booklet published by the Pediatric Dermatology Subspecialty Core
Group of the Philippine Dermatological Society entitled A Guide to
Understanding Moisturizers in Atopic Dermatitis summarizes the most
commonly accessible moisturizing products and grades the quality of
evidence supporting the efficacy and safety of their active ingredients.
Among the factors that may be considered in the choice of treatment
options for any case are the overall benefits perceived by the clinician
on these products, and the patients profile. Through analysis of these
factors, one may be able to determine the rationale for choosing the
best moisturizer options for the appropriate patient.
Treatment adherence is vital in primary and secondary prevention of
the symptoms of AD. Different strategies may be on hand to help a
clinician in the effort to promote reduction of flares and to improve
overall quality of life.
This booklet gives an overview of the status of moisturizer use in Asians
with AD based on the consensus points discussed during the 2014 Asian
Atopic Dermatitis Summit.
INTRODUCTION
Atopic dermatitis (AD) is a chronic pruritic inflammatory disorder characterized
as a defect in the skin barrier. This alteration in the barrier leads to increased
penetration by environmental allergens and infective organisms that cause
persistent inflammation in the skin. Although the barrier defect has been considered
in the past as an epiphenomenon, it is now believed to play a major role in the
pathophysiology of the disease.1 (Figure 1)2
External stimuli
Filaggrin mutation
Increased pH
Barrier disruption
Mechanical injury
Protease containing
protein antigen
exposure
Kallikrein activation
PAR-2 activation
TSLP upregulation
Th2 induction
FIGURE 1. Effect of barrier dysfunction on Th2 induction. Barrier dysfunction in line with filaggrin
deficiency will lead to Th2 skewing conditions, which may play an important role in the development
of AD
Legend: TSLP, thymic stromal lymphopoietin; Th2, T helper 2 cells; PAR-2, protease activated receptor-2
Reprinted from Journal of Dermatological Science, 70/1, Kabashima K, New concept of the pathogenesis of atopic dermatitis:
Interplay among the barrier, allergy, and pruritus as a trinity, Page No. 4, Copyright (2013), with permission from Elsevier.
FLARE
FLARE
FLARE
AD Severity
Time
Among the available treatment modalities, moisturizers are the most fundamental
requirement for optimal treatment of AD regardless of the severity.3 These
moisturizers hydrate the skin and repair skin barrier function.4 Worldwide, in all the
guidelines on management, moisturizer use is a key and basic step in the treatment
of AD. 3,5-11 (Figure 3)3
STEP 4 Systemic therapy (e.g. CyA) or UV therapy
t,
ran
cit AD
l
a
c
e
Re ever
s
e
rat D
de re A
o
E
M eve
s
AS
E
to
IS
to
OF
ld AD
Y
Mi rate
T
SI
de
mo
EN
IN
The severity of chronic diseases, especially AD, has a definite impact on the quality
of life (QOL) of both the patient and the family. As a result, certain priority patient
groups with similar disease morphologies have been considered to benefit from
specific moisturizer types. However, there remains to be a clinical classification
system to objectively determine which types of moisturizers are best suited for these
AD phenotypes. Products may be chosen according to whether these contain the
necessary ingredients (i.e. occulsives, humectants, or emollients) to match specific
profiles.
Dryness Scale
Healthy Skin
Slight Scaling
Severe Cracking
Key Opinion Leaders (KOLs) composed of specialists and subspecialists from allergy
and immunology, dermatology (paediatric and adult), and paediatrics from the Asia
Pacific region convened to work on a set of recommendations for the selection of
treatment options in AD that may be applicable within the region. More importantly,
the importance of moisturizers in the management strategy was highlighted, both in
the active and proactive treatment to attain the goal of controlling and preventing
the disease.
6
Occlusive
traps
water
H2O
H2O
H2O
H2O
H2O
Emollient
mimics
epidermal
lipids
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
Humectant
Water
Moisturizers restore the intercellular lipid bilayers ability to absorb, retain and
redistribute water by maintaining the integrity of the barrier.14,15 These agents may
penetrate and contribute to the reorganization of the structure of the skin layers.16
(Figure 5)
The effects of moisturizers can be measured using subjective and objective
parameters. However, the few trials that compare moisturizers have shown that it is
difficult to assess efficacy between products.17-19
There are several genes which contribute to skin types and mechanisms of repair
implying the presence of distinct atopic dermatitis phenotypes; however, is is
unknown which substrate (i.e. moisturizer ingredients) is necessary to address
the specific epidermal defect.20 The choice of moisturizers has therefore been
determined in clinical practice by individual preference, safety, efficacy, and absence
of fragrances, additives or other sensitizing agents.20
8
CLASSIFICATION OF MOISTURIZERS
There are several classes of moisturizers grouped according to their similar
characteristics and these are21:
(1) humectants, e.g. glycerine, 5 to 10% urea, lactic acid
(2a) occlusives, e.g. lipids, petrolatum, or liquid paraffin
(2b) emollients, e.g. fatty acids or cholesterol
These products are formulated in a variety of delivery systems including gels, oils,
creams, ointments, or lotions, and have different compositions and properties to
enhance efficacy.22 The following table summarizes the modes of action, properties,
and some representative agents from each class. (Table 1)23,24
Class
Mode of action
Biological
similarity
Some examples
Humectants
NMF in corneocytes
Glycerin
Alpha hydroxy acids Hyaluronic acid
Pyrrolidone carboxylic acid
Sodium pyrrolidone
carboxylic acid (Na PCA)
Sodium and ammonium lactate
Sorbitol
Urea
Occlusives
Form a hydrophobic
film to retard TEWL
of SC
Intercellular
lipid bilayers
- Ceramide
- Cholesterol
- Free fatty acids
Carnauba wax
Lanolin
Mineral oils
Olive oil
Petrolatum Silicone
Cetyl/stearyl alcohol Propylene glycol
Squalene
Stearic acid
Emollients
Smoothens skin
by filling the
cracks between
desquamating
corneocytes
Collagen
Colloidal oatmeal
Elastin
Glyceryl stearate
Isopropyl myristate/isostearate
Isopropyl palmitate
Isostearyl alcohol
Jojoba oil
Keratin
Lauric acid
Linoleic acid
Linolenic acid
Octyl octanoate/stearate
Oleic acid
Propylene glycol
Shea butter
Stearic acid
Legend: SC, subcutaneous layer; NMF, natural moisturizing factor; TEWL, transepidermal water loss
9
ANTI-INFLAMMATORY AGENTS
New anti-inflammatory agents are added into the formulation because of
their steroid-sparing effects.23 These agents include glycyrrhetinic acid, palmitoylethanolamine, telmesteine, Vitis vinifera, and ceramide-dominant barrier repair
lipids, and filaggrin breakdown products [e.g. ceramide precursor/pseudoceramide,
5-sphingosine derived sphingolipid, niacinamide, vitamin B3, pyrrolidone carboxylic
acid (PCA) and arginine].24
OH
O
HO
H3C
CH3
O
CH3
CH3
H
HO
H3C
OH
HO
Glycyrrhetinic
acid
H3C
Vitis vinifera
extract
OH
OH
HO
OH
CH3
H
H3C CH3
OH
HO
Telmesteine
H
N
OH
OH
0
S
HO
HO
OH
Ceramide
NH
O
Palmitoyl-ethanolamine
CH3
Of the available moisturizers with the above ingredients, a few have been
shown to provide effective control of xerosis and with rare adverse outcomes.24
MAS063DP (Atopiclair) cream, a non-steroidal hydrolipidic combination of
glycyrrhetinic acid, telmesteine, Vitis vinifera or grape seed extract, combined
with hyaluronic acid and shea butter, has been documented in adults and
children to have anti-inflammatory action on top of barrier repair features.25-27
10
RECOMMENDATIONS ON MOISTURIZER
USE
Guidelines have general recommendations on moisturizer use.3,13,24,43
These are:
FOR PATIENTS TO:
11
MOISTURIZER RECOMMENDATIONS BY
SPECIALTY GROUPS
The Pediatric Dermatology Subspecialty Core Group of the Philippine Dermatological
Society published a review of the evidence on specific moisturizer ingredients.24
Below is an abridged adaptation of their appraisal:
Active ingredient
Major category
Ceramide
Kernel oil
Emollient
Emollient
Shea butter
Filaggrin breakdown
product
PalmitoylEthanolamine
Sunflower oil
Glycyrrhetinic acid
Telmesteine
Vitis vinifera
Hyaluronic acid
Lactic acid
Propylene glycol
Urea
Mineral oil
Olive oil
Petrolatum
Virgin coconut oil
Notes
Level of
evidence
III
IIIb
Ib
IIb
IIb
Ib
Ib
Ib
Ib
Ib
IIIb
IIIb
IIb
No reports
No reports
IIIb
IIIb
TABLE 2. Common moisturizer ingredients with mechanisms and evidence supporting their use24
12
Legend: Ib, Individual randomized controlled trials (RCTs) with narrow confidence interval; IIb, Individual cohort study and low
quality RCT; III/IIIb, Individual case-control study
Occlusive
ointment, no water
Occlusive
emollient cream
Mild to
moderate AD
Occlusive
emollient ointment
Very severe AD
More severe AD
Priority patient
groups
Class
Definition
Usage
Mild to moderate AD
Occlusive emollient
cream
Oil-in-water emulsion to
prevent water evaporation
from the skin by providing a
film of lipid
More severe AD
Occlusive emollient
ointment
Water-in-oil emulsions
intended to provide a thicker
film of lipid on the skin.
Very severe AD
Occlusive ointment,
no water
White soft
Paraffin (WSP), liquid
paraffin (LP), 50:50 ratio of
the WSP/LP
Patient choice be
considered regarding the
thickness of barrier, variable
lipid content, severity of
condition, body site
Drier skin conditions
requiring a thicker lipid film.
Limited in use because of
patient acceptability
Very dry skin
Where simple
emollients are
ineffective or
greasier products are
unacceptable
Pruritic variants
Humectant
containing
emollients
Emollient product
containing humectants, urea
and glycerin, hold water in
the stratum corneum
Antipruritic emollient
Emollient products
containing
antipruritic agents
Pruritus
FIGURE 7. Dry skin groups and the recommended leave-on moisturizer types
13
PERSONAL
PREFERENCE
OR
Weather
conditions
Cost of treatment
Time of day that the
patient applies the
moisturizer
Cosmetic
acceptability
14
CONVENIENCE
The Panel also discussed
that it is important to consider:
Availability of products
over-the-counter
15
CLINICAL BASIS
The choice should not be based on
false economy, but on:
PATIENT
VALUES AND
PREFERENCES
CLINICAL
EXPERTISE
Clinical
Best
Practice
BEST
RESEARCH
EVIDENCE
Overall, until objective parameters identifying the best skin type for the choice of
moisturizers are developed, the decision to choose moisturizers will continue to
depend on the properties that physicians and their patients may find most beneficial
based on subjective considerations and outcomes.9,14
16
The cause or
trigger of AD
The clinical
manifestations
and features of AD
The laboratory
examinations necessary
for diagnosis
Treatment options,
skin care, and
environmental
management
The effects of these patient and caregiver education programs have been evaluated
in randomized controlled trials. Intervention groups in these studies were shown
to have positive improvement in the patients coping behaviour, sleeplessness
symptoms, anxiety about corticosteroid usage, and other psychological variables.
Hence, clinical outcomes may be improved by providing educational initiatives on
top of conventional treatments for AD.34-36
18
SMART GOALS
Another strategy to improve patient outcomes is by identifying specific, measurable,
attainable, relevant, and time-based (SMART) goals. Although originally used for
non-medical purposes39, this technique provides a structured guide for patients to
set treatment objectives to help manage chronic conditions.40,41 (Figure 8)
Relevant: How does the goal tie into your key responsibilities?
How is it aligned to objectives?
The objective may be written down in the patients personal journal. An example of
this plan as applied in AD is shown below42:
WHAT: The patient will be able to state the names of at least two of
the topical creams used currently and why he or she is using them.
WHY: To increase his or her knowledge about his or her illness
and assist with regimen adherence so that patient can function
independently.
WHEN: By the end of two weeks, the patient should be able to state
the names of the medications and verbalize the purpose for using
these topical creams.
20
Evidently, the healthcare providers involved in the care of patients can optimize
therapy by explaining the long term treatment plan, by being empathetic and
motivating, by being receptive to all queries from the patient and the caregiver, and
by scheduling follow-up appointments early on in order to discuss whether these
goals have been met or not.43
CONCLUSIONS
Overall management points that were outlined by the Panel include:
Compliance is of utmost importance and patient factors and
preference should always be taken into consideration when choosing
treatment for AD.
It is important to avoid cleansers with sodium lauryl sulphate, cetyl
alcohol, or strong sensitizers (e.g. bacitracin, neomycin, and polymyxin
B, lavender, etc).
Therapeutic patient education should be carried out.
Define goals that are patient-specific, measurable, achievable,
agreeable to patient, relevant, result-oriented, and time-limited
(SMART).
Promote activities to help build a good patient and doctor relationship,
eliciting concerns, requests, showing empathy and caring (e.g.
workshops).
Education of patients and their caregivers on the patients skin
condition and management is a key component of the strategies
(e.g. re-enforced nurse counselling, written action plan, patient
information leaflets, finger unit chart, written care instructions).
Treatment of AD should entail collaboration among the specialists
(e.g. dermatologists, paediatricians, allergists/immunologists,
pulmonologists, ENT, ophthalmologists) to address all interrelated
conditions of the patient (e.g. AD, asthma, allergic rhinitis, allergic
conjunctivitis, food allergy).
21
22
REFERENCES
1. Vijayanand P, Seumois G, Simspson LJ et al. Interleukin-4 production
by follicular helper T cells requires the conserved Il4 enhancer
hypersensitivity site V. Immunity 2012;36:175-87.
2. Kabashima K. New concept of the pathogenesis of atopic dermatitis:
Interplay among the barrier, allergy, and pruritus as a trinity. J
Dermatol Sci 2013;70:3-11.
3. Akdis CA, Akdis M, Bieber T, et al. Diagnosis and treatment of atopic
dermatitis in children and adults: European Academy of Allergology
and Clinical Immunology/American Academy of Allergy, Asthma and
Immunology/PRACTALL Consensus Report. J Allergy Clin Immunol
2006;118:152-69.
4. Simpson E, Dutronc Y. A new body moisturizer increases skin hydration
and improves atopic dermatitis symptoms among children and adults.
J Drugs Dermatol 2011;10:744-9.
5. NICE Pathways. Treatments for atopic eczema in children. Available
at
http://pathways.nice.org.uk/pathways/atopic-eczema-inchildren#path=view%3A/pathways/atopic-eczema-in-children/
treatments-for-atopic-eczema-in-children.xml&content=close.
Accessed 22/06/2014.
6. Ring J, Alomar A, Bieber T, et al. Guidelines for treatment of atopic
eczema (atopic dermatitis) part I. J Eur Acad Dermatol Venereol
2012;26:1045-60.
7. Ngan V, et al. Severe Atopic Dermatitis Management
Guideline. Available at http://www.healthhb.co.nz/wp-content/
uploads/2012/03/Severe-Atopic-Dermatitis-Management-Guideline.
pdf. Accessed 22/06/2014.
8. Australasian Society of Clinical Immunology and Allergy. Atopic
Dermatitis (Eczema). Available at http://www.allergy.org.au/healthprofessionals/hp-information/asthma-and-allergy/atopic-dermatitis.
Accessed 22/06/2014.
9. Lynde C, Barber K, Claveau J, et al. Canadian practical guide for the
treatment and management of atopic dermatitis. J Cutan Med Surg
2005;8 Suppl 4:1-9.
10. Sinclair W, et al. Guidelines on the management of atopic dermatitis
in South Africa. Available at http://www.derma.co.za/images/
Guidelines_on_the_management_of_atopic_dermatitis_in_South_
Africa.pdf. Accessed 22/06/2014.
11. Rubel D, Thirumoorthy T, Soebaryo RW, et al. Consensus guidelines for
the management of atopic dermatitis: an Asia-Pacific perspective. J
Dermatol 2013;40:160-71.
12. Schneider L, Tilles S, Lio P, et al. Atopic dermatitis: a practice
parameter update 2012. J Allergy Clin Immunol 2013;131:295-9.
13. Moncrieff G, Cork M, Lawton S. Use of emollients in dry-skin
conditions: consensus statement. Clin Exp Dermatol 2013;38:231-8;
quiz 238.
14. Kraft JN, Lynde CW. Moisturizers: what they are and a practical
approach to product selection. Skin Therapy Lett 2005;10:1-8.
15. Lynde CW. Moisturizers: what they are and how they work. Skin
Therapy Lett 2001;6:3-5.
16. Lodn M. Effect of moisturizers on epidermal barrier function. Clin
Dermatol 2012;30:286-96.
17. Rawlings AV, Canestrari DA, Dobkowski B. Moisturizer technology
versus clinical performance. Dermatol Ther 2004;17 Suppl 1:49-56.
18. Breternitz M, Kowatzki D, Langenauer M, et al. Placebo-controlled,
double-blind, randomized, prospective study of a glycerol-based
emollient on eczematous skin in atopic dermatitis: biophysical and
clinical evaluation. Skin Pharmacol Physiol 2008;21:39-45.
19. Peris K, Valeri P, Altobelli E, et al. Efficacy evaluation of an oil-inwater emulsion (Dermoflan) in atopic dermatitis. Acta Derm Venereol
2002;82:465-6.
20. Eichenfield LF, Tom WL, Berger TG, et al. Guidelines of care for the
management of atopic dermatitis: section 2. Management and
treatment of atopic dermatitis with topical therapies. J Am Acad
Dermatol 2014;71:116-32.
21. Arkwright PD, Motala C, Subramanian H, et al. Management of
difficult-to-treat atopic dermatitis. J Allergy Clin Immunol Pract
2013;1:142-51.
Faculty
Profiles
FACULTY PROFILES
A/Professor Maria Victoria Dizon
Department of Dermatology
College of Medicine & Surgery
University of Santo Tomas
Manila, Philippines
24
FACULTY PROFILES
Professor Adelaide Ann Hebert
25
FACULTY PROFILES
A/Professor Giam Yoke Chin
National Skin Centre
Singapore
Associate Professor Giam Yoke Chin is a Senior Consultant at the National Skin
Centre (NSC), Singapore and is the Advisor to the Paediatric Dermatology Division
at the NSC. A/Prof. Giam is also a clinical teacher at the National University of
Singapore and is a visiting consultant to the Paediatric Dermatology clinic at the
National University Hospital. Singapore. A/Prof. Giam received her medical and
doctoral degrees from the National University of Singapore. She underwent training
in various subspecialties of Dermatology and Paediatric Dermatology in the United
Kingdom at the University of Edinburgh (Royal Infirmary Edinburgh) and at St
Johns Institute of Dermatology. In the United States, she trained at the University
of Chicago (Illinois), Childrens Memorial Hospital (New York) and the University of
California, San Francisco (UCSF).
Her clinical and research interests include paediatric dermatology and skin health.
She is an Advisor to the Paediatric Dermatology Division, Education Committee at the
National Skin Centre in Singapore and sits on the Review Committee of Journal of
Philippines Dermatological Society. She is a reviewer for Annals Academy of Medicine
Singapore (AMS), the Singapore Medical Journal and Paediatric Dermatology (US).
26
FACULTY PROFILES
Professor Hardyanto Soebono
Faculty of Medicine
Gadjah Mada University
Yogyakarta, Indonesia
27
FACULTY PROFILES
Dr Inne Arline Diana
Dr Inne Arline Diana is Head of the Division of Paediatric Dermatology at the Dr Hasan
Sadikin Hospital, Bandung, Indonesia. She earned her medical degree and trained
as a dermato-venereologist at the Faculty of Medicine, University of Padjadjaran,
Bandung, Indonesia. Dr Diana underwent further training in paediatric dermatology
at the Academic Medical Center, University of Amsterdam, the Netherlands and in
pigmentary disorders at the Netherlands Institute for Pigmentary Disorders. She
also underwent training in phototherapy at the National Skin Centre, Singapore.
Dr Diana is a member of the Indonesian Medical Association, Indonesian Society
of Dermatology and Venereology, International Society of Dermatologic Surgery,
American Society of Dermatologic Surgery, Dermatology and Aesthetic Surgery
International League and is the Chairman of Indonesian Paediatric Dermatology
Study Group.
28
FACULTY PROFILES
Professor Kyu-Han Kim
Department of Dermatology,
Seoul National University Hospital,
Seoul, Korea
29
FACULTY PROFILES
Dr David Luk Chi Kang
30
FACULTY PROFILES
Dr Zakiudin Munasir
31
FACULTY PROFILES
A/Professor Marysia Tiongco-Recto
Section of Allergy and Immunology
Department of Paediatrics
University of the Philippines
Manila, Philippines
32
FACULTY PROFILES
Professor Hugo Van Bever
Professor Hugo van Bever is Professor and Senior Consultant at the Division of
Paediatric Allergy, Immunology and Rheumatology, Khoo Teck Puat-National
University Childrens Medical Institute, Singapore. He obtained his medical degree
at the State University of Ghent, Belgium where he also completed his paediatrics
training at the Childrens Hospital. He continued his training in paediatric allergy and
pulmonology at the University of Antwerp, Belgium, where he eventually became
Professor in Paediatric Allergy and Pulmonology and Head of the Department of
Paediatrics before moving to Singapore.
His areas of clinical research and interest include paediatric allergy, asthma and
respiratory infections. His current research is focused on eczema, allergic rhinitis,
sublingual immunotherapy, primary prevention of allergy and food allergy.
Prof. van Bever is a member of various national and international societies, including
the European Academy of Allergy and Clinical Immunology (EAACI), the American
Academy of Allergy, Asthma and Immunology (AAAAI), the European Society of
Paediatric Allergy and Clinical Immunology (ESPACI), and the European Respiratory
Society (ERS). He is Past Secretary of the Group Paediatric Asthma and Allergy of
the ERS, Past Secretary of The Belgian Society of Allergy and Clinical Immunology
(BELSACI) and Board Member of The Flemish Group of Allergologists. He is a longstanding member of the Asian Pacific Association of Paediatric Allergy, Respirology
and Immunology (APAPARI).
Prof. van Bever has published more than 300 papers in national and international
journals. He is a member of the Editorial Board of Paediatric Allergy, Asian Pacific
Journal of Allergy and Immunology and is Editor in Chief of the Journal of Allergy.
Prof. van Bever is a reviewer for the European Journal of Paediatrics, Paediatrics,
Paediatric Allergy and Immunology, Allergy, Paediatric Pulmonology, the European
Respiratory Journal, Paediatric Research, British Medical Journal, the American
Journal of Respiratory and Critical Care Medicine and Archives of Diseases in
Childhood.
IBC