Better Treatment and Prevention of Atopic Eczema
Submitting InstitutionUniversity of Sheffield
Unit of AssessmentAllied Health Professions, Dentistry, Nursing and Pharmacy
Summary Impact TypeHealth
Research Subject Area(s)
Medical and Health Sciences: Immunology
Summary of the impact
Research investigating genetic and environmental interactions leading to
skin barrier breakdown in atopic eczema has delivered health benefits by
improving the prevention and treatment of this condition. We found that
established emollient formulations (e.g. Aqueous Cream BP) containing the
harsh emulsifier sodium lauryl sulphate (SLS) damage the skin barrier in
patients with atopic eczema and identified an underlying molecular
mechanism. Consequently, the NICE Quality Standard and Guidelines now
reflect our advice that Aqueous Cream should not be used as a leave-on
emollient, SLS has been removed from all emollient formulations in the UK
and we have helped develop the next generation of `SLS-free' skin-care
products. Medicines regulators including the Medicines and Healthcare
products Regulatory Agency (MHRA) and New Zealand MedSafe have also issued
new advice as a result of our research.
Research led by Professor Cork (University of Sheffield since 1995) and
Dr Tazi-Ahnini (University of Sheffield since 2000) in the Academic Unit
of Dermatology identified genetic and environmental factors that lead to
skin barrier breakdown in atopic eczema (atopic dermatitis). Studies
showed that an increase in protease activity within the upper layers of
the skin, attributable to genetic variants in protease and protease
inhibitor genes, contributes to a major breakdown of skin barrier function
[R1, R2, R3].
These researchers also observed that harsh soaps and the use of Aqueous
cream BP (`Aqueous Cream') containing the detergent sodium lauryl sulphate
(SLS) were associated with poor control of disease in children with atopic
eczema. An audit of the number of cutaneous reactions to different types
of emollient creams including Aqueous Cream showed that 56% of episodes of
exposure to Aqueous Cream were associated with burning, stinging and
redness of the skin, compared to 18% for all other emollients [R4].
This led to the conclusion that the SLS in Aqueous Cream was damaging the
skin barrier and making the atopic eczema worse rather than better.
Further research demonstrated that Aqueous Cream also caused severe damage
to the skin barrier in people with a previous history of atopic
dermatitis. SLS raises the pH of the upper layers of the skin leading to
enhanced protease activity [R5], explaining why it causes
exacerbation rather than improvement of symptoms [R4]. The increase
in pH also inhibits the synthesis of the lipid lamellae, further worsening
skin barrier dysfunction [R5]. These factors therefore feed a
common pathway in skin barrier breakdown and the development of atopic
Education regarding the avoidance of harsh soap and detergents and the
use of emollients is the first line therapy of atopic eczema. It was
demonstrated that comprehensive education of parents and children with
atopic eczema was essential in order to ensure avoidance of damaging
environmental agents and correct use of emollients [R6].
The underpinning research has therefore identified genetic and
environmental factors that lead to skin barrier breakdown in atopic
eczema, has led to the development of new optimal emollient formulations
and wash-products, and has provided education on how to use topical
treatment to improve the treatment and prevention of atopic eczema
References to the research
R1. Vasilopoulos Y, Cork MJ, Murphy R, Williams HC, Robinson DA,
Duff GW, Ward SJ, Tazi-Ahnini R. (2004). Genetic association between an
AACC insertion in the 3'UTR of the stratum corneum chymotryptic enzyme
gene and atopic dermatitis. Journal of Investigative Dermatology.
123: 62-66. doi: 10.1111/j.0022-202X.2004.22708.x
R2. Vasilopoulos Y, Cork MJ, Teare D, Marinou I, Ward SJ, Duff GW,
Tazi-Ahnini R. (2007). A nonsynonymous substitution of cystatin A, a
cysteine protease inhibitor of house dust mite protease, leads to
decreased mRNA stability and shows a significant association with atopic
dermatitis. Allergy. 62: 514-519. doi: 10.1111/j.1398-9995.2007.01350.x
R3. Vasilopoulos Y, Sharaf N, di Giovine F, Simon M, Cork MJ, Duff
GW, Tazi-Ahnini R. (2011). The 3'-UTR AACCins5874 in the stratum corneum
chymotryptic enzyme gene (SCCE/KLK7), associated with atopic dermatitis;
causes an increased mRNA expression without altering its stability. Journal
of Dermatological Science. 61: 131-3. doi: 10.1016/j.jdermsci.2010.11.013
R4. Cork MJ, Timmins J, Holden C, Carr J, Berry V, Tazi-Ahnini R,
Ward SJ. (2003). An audit of adverse drug reactions to aqueous cream in
children with atopic eczema. Pharmaceutical Journal. 271: 747-748.
R5. Danby S, Al Enezi T, Sultan A, Chittock J, Kennedy K, Cork MJ.
(2011). The effect of aqueous cream BP on the skin barrier in volunteers
with a previous history of atopic dermatitis. British Journal of
Dermatology. 165: 329-334. doi: 10.1111/j.1365-2133.2011.10395.x
R6. Cork MJ, Britton J, Butler L, Young S, Murphy R, Keohane SG.
(2003). Comparison of parent knowledge, therapy utilization and severity
of atopic eczema before and after explanation and demonstration of topical
therapies by a specialist dermatology nurse. British Journal of
Dermatology. 149: 582-589. doi: 10.1046/j.1365-2133.2003.05595.x
Details of the impact
Impact on health
The National Eczema Society (NES) charity, which supports people with
eczema, highlights the substantial improvements to eczema patient
wellbeing that have resulted from our work [S1, S2].
Recommendations by NICE agreed with the conclusions that Aqueous Cream BP
should never be used as a leave-on emollient; the NICE guidance on atopic
eczema in children [S3] cited this research. This advice has been
further reinforced in the NICE Quality Standard for atopic eczema issued
in 2013 [S4], which is based on the NICE atopic eczema guideline of
Our Aqueous Cream research has also been recognised and acted upon by
medicine regulators internationally. The New Zealand Medicines Safety
Authority quoted R5 stating. "These papers highlight the importance of
not using products containing SLS, such as Aqueous Cream, as leave-on
emollients as they may act to exacerbate skin damage, rather than
support skin barrier function" [S5]. Other regulators
including the Medicine and Healthcare products Regulatory Agency (MHRA)
have issued advice regarding the adverse effects of Aqueous Cream [S6].
As a result of these research-led changes, the costs of healthcare have
changed in practice. The NES has followed our research using it in their
campaign to remove cheap, ineffective, harmful emollients, such as Aqueous
Cream, from formularies. "These products not only exacerbate diseases
such as atopic eczema but may even contribute to its development. They
are also a false economy because Aqueous cream often makes atopic eczema
worse leading to referral to dermatologists" [S1, S2]. The
sales of Aqueous Cream have fallen 70% since 2009 [S1].
All of the UK companies previously producing emollients containing SLS
have now removed the SLS and replaced it with a less harmful emulsifier.
NES sources state that: "The logo `SLS Free' now appears on all of
these emollients — a direct consequence of your research. Similar
reformulations of emollient products are taking place internationally"
As a result of our research, companies producing skin-healthcare products
have invested in research and development, working with us to design and
test new and improved formulations that are now in production. We have
spent the past 15 years developing completely new products to produce an
optimal repair of the defective skin barrier in atopic dermatitis,
initially through a spinout company (Molecular Skin Care), but more
recently with a [text removed for publication] investment by [text removed
for publication] [S7]. We have performed randomised control
clinical studies demonstrating the benefits of the new formulation
compared with existing formulations. This product is now going into
production [S1, S2].
We have also been working with other pharmaceutical companies to develop
optimal wash products, for use in regimens to prevent the development of
atopic eczema. We have worked with Johnson & Johnson to develop and
test an optimally formulated SLS-free range of baby care products
(including `Top to Toe' baby wash). Johnson and Johnson funded a knowledge
exchange scheme (£718,000) with the University of Sheffield to exploit
biochemical and biophysical assays of skin barrier function developed by
the group [S8]. With our collaborators (Professor Dame Tina
Lavender's group in Manchester) and Johnson and Johnson in the USA we have
conducted a programme of clinical trials to evaluate all of the products
that we put on babies' skin [S9, S10]. Since 2008, Johnson and
Johnson have invested many £millions in research and development of these
products and have seen sales of their products `Top-To-Toe Bath' increase
by 15% and `Extra Sensitive Wipes' increase by 8% [S8]. The key
enabler in these sales increases was verification of the findings from the
clinical trials that these products were safe to use from birth.
Public understanding has improved. Educating children with atopic
eczema and their parents regarding the importance of avoiding all harsh
soaps and detergents, and how to use the correct emollient products, was
evaluated in our 2003 audit [R6]. This paper was cited by both NICE
2007 and NICE 2013 as evidence for the crucial role of education in the
treatment of atopic eczema [S3, S4]. Regarding our work NES states
that: "Education regarding the use of topical treatments is one of the
interventions that has transformed the lives of children and adults with
atopic eczema. The Sheffield team, led by Professor Michael Cork, have
made a major contribution in this area" [S1, S2].
Sources to corroborate the impact
S1. CEO of The National Eczema Society (NES) support
letter (on file).
S3. NICE Atopic Eczema Guidelines, CG57-issued December 2007
Although published in 2007, this guideline remains valid. There have been
S4. NICE Quality Standards 44, Atopic Eczema in Children published
September 2013. Full guidance is found here: http://guidance.nice.org.uk/QS44.
Specific guidance on avoidance of sodium lauryl sulphate containing
emollient is found here: http://tinyurl.com/okra5rj
S5. New Zealand Medicines and Medical Devices Safety Authority (NZ
MEDSAFE) Aqueous Cream — Moisturiser or Irritant? March 2012; Prescriber
Update 2012; 33(1): 4.
S6. MHRA UK Public Assessment Report (March 2013). Aqueous cream:
may cause skin irritation, particularly in children with eczema, possibly
due to sodium lauryl sulfate content. Drug Safety Update, volume 6,
issue 8, Article A2.
S7. [text removed for publication] support letter (on file)
regarding the development of optimal emollient formulations.
S8. Johnson & Johnson support letters (on file). Details of
the partnership between the University of Sheffield and J&J are
described, including figures for investment in Research and Development
and the impact of research on sales of J&J baby skin care products.
S9. Lavender T, Bedwell C, O'Brien E, Cork MJ, Turner M, Hart A.
Infant skin-cleansing product versus water: A pilot randomized,
assessor-blinded controlled trial. BMC Pediatr. 2011 May 13;
11:35. doi: 10.1186/1471-2431-11-35
This pilot study (n=100 randomised to 2 groups) provided data to inform an
extensive trial of Johnson and Johnson's® baby top-to-toe™ wash.
S10. Lavender T, Bedwell C, Roberts SA, Hart A, Turner MA, Carter
LA, Cork MJ. Randomized, Controlled Trial Evaluating a Baby Wash Product
on Skin Barrier Function in Healthy, Term Neonates. J Obstet Gynecol
Neonatal Nurs. 2013 Feb 19. doi: 10.1111/1552-6909.12015.
Newborn bathing with baby top-to-toe™ wash product (n=159) was
compared to water alone (n=148) in a powered, randomised, trial. No
difference was found between the two regimes and the data can be used to
reassure and inform parental choice of wash protocols.