Hong Kong Med J 2015 Oct;21(5):417–25 | Epub 28 Aug 2015
DOI: 10.12809/hkmj144472
ORIGINAL ARTICLE
Patient acceptability, efficacy, and skin biophysiology of a cream and cleanser containing lipid complex with shea butter extract versus a ceramide product for eczema
KL Hon, MD, FCCM1; YC Tsang, BSc1; NH Pong, MPhil1; Vivian WY Lee, PharmD2; NM Luk, FRCP3; CM Chow, FRCPCH1; TF Leung, FRCPCH, FAAAAI1
1 Department of Paediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong
2 School of Pharmacy, The Chinese University of Hong Kong, Shatin, Hong Kong
3 Hong Kong Dermatology Foundation, Hong Kong
Corresponding author: Prof KL Hon (ehon@hotmail.com)
 
 Full paper in PDF
Abstract
Objectives: To investigate patient acceptability, efficacy, and skin biophysiological effects of a cream/cleanser combination for childhood atopic dermatitis.
 
Design: Case series.
 
Setting: Paediatric dermatology clinic at a university teaching hospital in Hong Kong.
 
Patients: Consecutive paediatric patients with atopic dermatitis who were interested in trying a new moisturiser were recruited between 1 April 2013 and 31 March 2014. Swabs and cultures from the right antecubital fossa and the worst eczematous area, disease severity (SCORing Atopic Dermatitis index), skin hydration, and transepidermal water loss were obtained prior to and following 4-week usage of a cream/cleanser containing lipid complex with shea butter extract (Ezerra cream; Hoe Pharma, Petaling Jaya, Malaysia). Global or general acceptability of treatment was documented as ‘very good’, ‘good’, ‘fair’, or ‘poor’.
 
Results: A total of 34 patients with atopic dermatitis were recruited; 74% reported ‘very good’ or ‘good’, whereas 26% reported ‘fair’ or ‘poor’ general acceptability of treatment of the Ezerra cream; and 76% reported ‘very good’ or ‘good’, whereas 24% reported ‘fair’ or ‘poor’ general acceptability of treatment of the Ezerra cleanser. There were no intergroup differences in pre-usage clinical parameters of age, objective SCORing Atopic Dermatitis index, pruritus, sleep loss, skin hydration, transepidermal water loss, topical corticosteroid usage, oral antihistamine usage, or general acceptability of treatment of the prior emollient. Following use of the Ezerra cream, mean pruritus score decreased from 6.7 to 6.0 (P=0.036) and mean Children’s Dermatology Life Quality Index improved from 10.0 to 8.0 (P=0.021) in the ‘very good’/‘good’ group. There were no statistically significant differences in the acceptability of wash (P=0.526) and emollients (P=0.537) with pre-trial products. When compared with the data of another ceramide-precursor moisturiser in a previous study, there was no statistical difference in efficacy and acceptability between the two products.
 
Conclusions: The trial cream was acceptable in three quarters of patients with atopic dermatitis. Patients who accepted the cream had less pruritus and improved quality of life than the non-accepting patients following its usage. The cream containing shea butter extract did not differ in acceptability or efficacy from a ceramide-precursor product. Patient acceptability is an important factor for treatment efficacy. There is a general lack of published clinical trials to document the efficacy and skin biophysiological effects of many of the proprietary moisturisers.
 
New knowledge added by this study
  • Patient acceptability is an important factor for treatment efficacy.
Implications for clinical practice or policy
  • There is a general lack of published clinical trials to document the efficacy and skin biophysiological effects of many of the proprietary moisturisers.
 
 
Introduction
Eczema or atopic dermatitis (AD) is a chronically relapsing dermatosis associated with atopy, and characterised by reduced skin hydration (SH), impaired skin integrity (transepidermal water loss [TEWL]), and poor quality of life as a result of deficient ceramides in the epidermis.1 Regular application of a moisturiser is the key step in its management. Moisturiser therapy for AD is significantly complicated by the diversity of disease manifestations and by a variety of complex immune abnormalities.1 Filaggrin (filament-aggregating protein) and related moisturising factors have an important function in epidermal differentiation and barrier function, and null mutations within the filaggrin gene are major risk factors for developing AD.2 3 4 5 6 Ceramides and related lipid products are also important components in skin barrier function.7 Recent advances in the understanding of the pathophysiological process of AD have led to the production of new moisturisers targeted at correcting the reduced amount of ceramides and natural moisturising factors in the stratum corneum with ceramides, pseudoceramides, or natural moisturising factors.7 Many proprietary products claim to have these ingredients, but have no or limited studies to document their clinical efficacy. Our group previously tested a number of these commercial products and found patient preference and acceptability may influence outcomes of topical treatment independent of the ingredients in these products.8 The purposes of this study were to investigate patient acceptability of a cream/cleanser combination containing lipid complex and shea butter extract with claimed antihistaminergic properties, and evaluate its efficacy in improving the clinical and biophysiological properties of the skin in AD patients. A MEDLINE search was also performed to evaluate whether evidence of efficacy of many of the proprietary moisturisers exists.
 
Methods
Consecutive patients with AD who were interested in trying a new moisturiser were recruited from the paediatric dermatology clinic at a university teaching hospital in Hong Kong. Diagnosis of AD was based on the UK working group criteria.9 In this study, SH and TEWL in the right forearm (2 cm below the antecubital flexure), and disease severity (SCORing Atopic Dermatitis [SCORAD] index) were measured. We have previously described our method of standardising measurements of SH and TEWL.10 After acclimatisation in the consultation room with the patient sitting comfortably in a chair for 20 to 30 minutes, SH (in arbitrary units) and TEWL (in g/m2/h) were then measured according to the manufacturer’s instructions with the Mobile Skin Center MSC 100 equipped with a Corneometer CM 825 (Courage + Khazaka electronic GmbH, Cologne, Germany), and a Tewameter TM 210 probe (Courage + Khazaka electronic GmbH). We documented that a site 2 cm distal to the right antecubital flexure was optimal for standardisation. Oozing and infected areas were avoided by moving the probe slightly sideways.10 The clinical severity of AD was assessed with the SCORAD index.11 12 The SCORAD index also scores pruritus and sleep loss/disturbance on a scale of 0 to 10 (0 being not affected and 10 being most severely affected).
 
Patients were given a liberal supply of a trial cream containing lipid complex with shea butter extract for eczema (Ezerra [E]; Hoe Pharma, Petaling Jaya, Malaysia) and body wash (E, Hoe Pharma). The moisturiser contained STIMU-TEX AS (Centerchem Inc, Norwalk [CT], US) and saccharide isomerate. The wash contained STIMU-TEX AS and Amisoft (Amisoft Technologies Ltd, Brentwood, UK). The patients were instructed not to use any other moisturiser or topical treatment. Use of any medications such as topical corticosteroid or oral antihistamine was documented. Patients were encouraged to use the test moisturiser at least twice daily on the flexures and areas with eczema. In case the emollient effect was not satisfactory, they could use their usual emollient and medications, but the frequency of such use was to be reported and they must continue with the E moisturiser. The patients were reviewed at the end of 4 weeks. Measurements of SCORAD index, Children’s Dermatology Life Quality Index (CDLQI), SH, and TEWL were repeated. Patients’ global or general acceptability of treatment (GAT) was recorded as ‘very good’, ‘good’, ‘fair’, or ‘poor’.8 13 Approval was obtained from the Clinical Research Ethics Committee of the Chinese University of Hong Kong and written informed consents were obtained from the guardian and patient.
 
Continuous data were expressed as mean and standard deviation. Mann-Whitney U test was used for intergroup comparison and Wilcoxon signed rank test for within-group comparison as a small number of patients was included. Categorical data were presented in counts. Chi squared test or Fisher’s exact test where appropriate was used to compare intergroup categorical data, while McNemar’s test was used to compare within-group categorical data. Fisher’s exact test was used to determine the GAT of previously used proprietary products and E moisturiser and wash. All comparisons were two-tailed, and P values of <0.05 were considered to be statistically significant. The results were also compared with the data for an emollient (C) containing ceramide-precursor lipids and moisturising factors (n=24).14
 
Results
Between 1 April 2013 and 31 March 2014, 34 patients (56% boys; mean [± standard deviation] age, 12.1 ± 4.4 years) with AD were recruited and treated with applications of a moisturising cream (E). Compliance was good and patients generally managed to use the moisturiser daily. Among the patients, 74% reported ‘very good’ or ‘good’ acceptability, whereas 26% reported ‘fair’ or ‘poor’ acceptability of the moisturiser (Tables 1 and 2).
 

Table 1. Global acceptability of treatment (GAT) of cream/cleanser containing lipid complex (E)
 

Table 2. Acceptability and efficacy of Ezerra cream containing lipid complex
 
There were no intergroup differences in pre-usage clinical parameters of age, objective SCORAD index, pruritus, sleep loss, SH, TEWL, topical corticosteroid usage, oral antihistamine usage, or GAT of prior emollient (Table 2). Following use of the E cream, pruritus score and CDLQI were lower in the ‘very good’/‘good’ group than in the ‘fair’/‘poor’ group. Mean pruritus score decreased from 6.7 to 6.0 (P=0.036) and mean CDLQI improved from 10.0 to 8.0 (P=0.021) in the ‘very good’/‘good’ group (Table 2).
 
When analysed for the association of the rating of acceptability, the acceptability of E cleanser (P=0.526) and E cream (P=0.537) was not significantly associated with their respective pre-trial products (Table 1). Patients who preferred the trial moisturiser or wash might or might not have come from the group of poor/fair acceptability of their prior emollient or wash, and vice versa. Prior products included emulsifying ointment and various other proprietary products.
 
When compared historically with another product containing ceramide-precursor lipids (C) that we tested in a previous report,14 the present shea butter extract–containing cream showed similar efficacy and acceptability (Table 3). It appears that ceramide does not confer superiority in terms of acceptability and clinical efficacy.
 

Table 3. Comparative study of the cream containing lipid complex (E) with a proprietary emollient containing ceramide-precursor lipids (C)
 
A MEDLINE search was performed on selected common proprietary moisturisers/emollients for eczema using the following search terms in combinations: “eczema” OR “atopic dermatitis”, AND “emollient” OR “moisturizer” OR “barrier” OR “barrier repair” OR “natural moisturizing factor” OR “ceramide” OR “pseudoceramide”. We selected literature mainly from the past 10 years, but did not exclude commonly referenced and highly cited older articles. We included and described all randomised trials, case series, and bench studies in barrier repair therapy for eczema, with limits activated (Humans, Clinical Trial, Meta-Analysis, Randomized Controlled Trial, English, published in the past 10 years). Editorials, letters, practice guidelines, reviews, and animal studies were excluded. In addition, the bibliographies of the retrieved articles and our own research database were also hand searched. As of 23 April 2014, 18 articles were obtained (Table 413 27 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48). The common proprietary moisturisers were included. The publications generally provided limited evidence of efficacy and biophysical effects (such as SH and TEWL), but virtually no data on patient acceptability and effects on Staphylococcus aureus colonisation.
 

Table 4. Results of a MEDLINE search of studies of selected proprietary moisturisers13 27 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48
 
Discussion
Atopic dermatitis is a chronically relapsing dermatosis characterised by pruritus, skin dryness, inflammation, secondary bacterial infection by S aureus, and poor quality of life.1 15 16 17 The stratum corneum normally consists of fully differentiated corneocytes surrounded by natural moisturising factor and a lipid-rich matrix containing cholesterol, free fatty acids, and ceramide. In AD, metabolism of lipid and filaggrin protein is abnormal, causing a deficiency of ceramide and natural moisturising factors and impairment of epidermal barrier function that leads to increased TEWL and abnormal skin integrity.1 4 7 18 19 20 21 Moisturisers form the first-line therapy as maintenance and therapeutic management in childhood-onset AD.1 22 23 Hydration of the skin helps to improve dryness, reduce pruritus, and restore disturbed barrier function. Bathing without the use of moisturiser may compromise SH.24 25 26
 
In this study, we explored clinical efficacy and acceptability of a proprietary moisturiser (E) containing shea butter extract. The cream was acceptable as ‘very good’ or ‘good’ in about three quarters of patients with AD who tried the moisturiser, and ameliorated their pruritus and improved their quality of life.
 
Compliance or adherence to usage of the moisturising cream was reflected by the GAT and reported frequency of usage (times per day).27 We did not calculate the amount of moisturising cream used because many parents/patients have discarded the tubes or failed to bring them back for weighing in previous trials. Topical steroid usage is also an important confounding factor in this study. We standardise treatment for all our patients by not changing their existing topical steroid (mometasone furoate) and other medications (ie oral antihistamine, topical immunomodulant, and Chinese medicine). In previous studies, we found that documentation of the exact amount of steroid usage (weight or frequency of usage) was difficult for similar reasons as those for moisturisers.28 Most parents are still concerned about topical steroid usage and tend to use the minimal amount of steroid as far as possible.29
 
Alternative explanations for the modest within-group changes in pruritus and CDLQI (Table 2) include regression to the mean, detection bias, or confounding by co-treatment with topical corticosteroid or usual emollients. Our study did not demonstrate any reduction in clinical severity or S aureus colonisation. When compared historically with another product (C) containing ceramide-precursor lipids that we tested in a previous report,14 although different patients were involved and the E or C products were not received by patients in the same period, the present E cream showed similar efficacy and acceptability with the use of a similar study protocol as the previous study. It appears that specific ceramide-precursor lipids do not confer superiority in terms of acceptability and clinical efficacy.
 
Regarding intra-group comparisons, the C cream reduced objective SCORAD index (P=0.027) and increased SH (P=0.015), whereas the E cream reduced pruritus and improved CDLQI only in the ‘very good’/‘good’ group (Table 3). Regarding intergroup comparisons, overall there were no significant differences between the pretreatment and post-treatment parameters for the two moisturisers. We note that in the subgroup analysis, pruritus and CDLQI could be the possible contributing factors for the acceptability in the ‘very good’/‘good’ group for the E cream.
 
Many proprietary emollients/moisturisers are available in the market.7 22 30 31 Despite claims about their efficacy, little evidence has demonstrated the short- or long-term usefulness of many of these proprietary products. Ceramides, pseudoceramides, or filaggrin protein products have been studied and added to commercial moisturisers to mimic natural skin lipids and moisturising factors.32 Anxious parents often consult their physicians for recommendation as to the choice of an ideal or perfect moisturiser for their child with AD. Physicians need to have some evidence-based understanding about these moisturisers in order to address issues raised by the parents. We performed a MEDLINE search and found that only a few of these products have published clinical data (Table 413 27 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48). The majority either do not have patient acceptability or clinical efficacy data in the scientific literature. The efficacy of ceramides and natural moisturiser factors is generally not scientifically documented. Larger-scale, properly conducted randomised controlled trials with recruitment of more study participants may validate subtle differences in clinical efficacy between different emollients. It is likely that there will be similar outcomes in efficacy if the tested emollient is compared with any other traditional emollient such as aqueous cream or Vaseline (Unilever, London, England). Commercial pharmaceutical companies are often unwilling to supply free samples of their product to compare with an inexpensive product, even if more validated and conclusive results may be obtained by increasing the sample size in clinical trials. That is perhaps why there are so few comparative clinical studies in the medical literature.
 
In a wider context, AD is a complex multifactorial atopic disease. Monotherapy targeting merely at replacement of ceramides, pseudoceramides, or filaggrin degradation products at the epidermis is often suboptimal. In particular, colonisation with S aureus must be adequately treated before emollient treatment can be optimised.17
 
The major hindrance to the efficacy of a moisturiser is the patient’s perception as to what an ideal moisturiser should be.8 Indeed, it is often not the product, but the patient’s acceptability that determines whether it may be used consistently. Therefore, the physician caring for a patient with AD must educate and guide the parents and the patient to choose the most acceptable formulation to ensure optimal compliance.
 
This open-label series confirms our previous experience in emollient research. First, patient acceptance of the strengths, types, and formulations of any novel products need to be studied, preferably in randomised controlled trials. Second, holistic efficacy studies of all clinical parameters (namely severity scores, quality-of-life indices, SH, TEWL, S aureus colonisation, and patient acceptance) must be included. Third, as AD is not a simple epidermal skin disease but rather a complex atopic disease, emollient alone is bound to be suboptimal in efficacy.
 
Conclusions
Well-designed, large-scale, randomised, placebo-controlled trials to document therapeutic effects on disease severity, skin biophysiological parameters, quality of life, and patient acceptability are needed. Patient’s acceptability of a certain product is pivotal for compliance and clinical outcome. Only few of the many proprietary moisturisers for AD have undergone clinical trials to evaluate clinical efficacy and patient acceptability.
 
Declaration
Drs KL Hon and TF Leung have performed research on eczema therapeutics, and written about the subject matter of filaggrin, ceramides, and emollients.
 
Acknowledgements
We thank Hoe Pharma in Hong Kong for freely supplying the studied materials. The company, however, was not involved in the design or analysis of the research data. The products used in the present study could be examples of other similar products containing shea butter.
 
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