Abstract
Aim
To review current classes of emollients in the market, their clinical efficacy in atopic dermatitis (AD) and considerations for choice of an emollient.
Methods
PubMed Clinical Queries under Clinical Study Categories (with Category limited to Therapy and Scope limited to Narrow) and Systematic Reviews were used as the search engine. Keywords of ‘emollient or moisturizer’ and ‘atopic dermatitis’ were used.
Overview of findings
Using the keywords of ‘emollient’ and ‘atopic dermatitis’, there were 105 and 36 hits under Clinical Study Categories (with Category limited to Therapy and Scope limited to Narrow) and Systematic Reviews, respectively. Plant-derived products, animal products and special ingredients were discussed. Selected proprietary products were tabulated.
Conclusions
A number of proprietary emollients have undergone trials with clinical data available on PubMed-indexed journals. Most moisturizers showed some beneficial effects, but there was generally no evidence that one moisturizer is superior to another. Choosing an appropriate emollient for AD patients would improve acceptability and adherence for emollient treatment. Physician’s recommendation is the primary consideration for patients when selecting a moisturizer/emollient; therefore, doctors should provide evidence-based information about these emollients.
Keywords: atopic dermatitis, emollient
Introduction
Atopic dermatitis (AD) is a complex disease with various degrees of skin inflammation, erythema, dryness and staphylococcal infections [1,2]. The cardinal symptoms are pruritus and sleep disturbance, and quality of life is much affected. The mainstay of treatment for AD is regular usage of emollient and topical medications [3]. Emollients provide an occlusive barrier for AD skin, retain moisture and protect it from irritants. Specially formulated emollient products may claim to have antimicrobial, anti-itch and anti-inflammatory actions. They are complex mixtures of chemical agents specially designed to make the epidermis softer and more pliable [4,5]. However, ‘emollient’ sometimes refers to a specific ingredient that soothes the skin; it is more appropriate to use the term ‘moisturizer’. The terms ‘emollients’ and ‘moisturizers’ are often used interchangeably. Occlusive agents work by forming a thin hydrophobic film on the surface of the skin to retard transepidermal loss of moisture [4]. They are similar to the intercellular lipid bilayers of ceramide, cholesterol and free fatty acids [4,5]. Examples include lanolin, mineral oils, olive oil, petrolatum ceramide, paraffin and silicone. Humectants attract water vapor to moisturize the skin [4]. They are similar to the natural moisturizing factors in the corneocytes. Examples include glycerin, alpha hydroxyl acids and sorbitol. Emollients fill the cracks between desquamating corneocytes and smoothen the skin [4]. Examples include collagen, elastin, glyceryl stearate and shea butter [6].
Choosing an emollient has been a major concern for patients and physicians. Despite price differences, the major ingredients of an emollient are similar, consisting of petrolatum, paraffin, glycerin, plant-derived butter and oils, and their combinations provide various formulations for the market [7,8]. Recent advances in the understanding of the pathophysiology of AD have led to the production of new moisturizers targeted to replenish ceramides and natural moisturizing factors in the stratum corneum [9]. Many brands of emollients are expensive and claim to contain ingredients targeting AD pathophysiology [5]. A number of these emollients have not been subjected to vigorous scientific evaluations to document their clinical efficacy or relevance. Parents are constantly in search of an ideal emollient that they will find acceptable for use on their children [7]. We previously tested a number of commercial products and noted patient factors – namely, preference and acceptability – may influence outcomes of topical treatment independent of ingredients in these products [7].
This overview aims to discuss current classes of emollients in the market, clinical evidence and considerations for choice of an emollient.
Methods
PubMed Clinical Queries under Clinical Study Categories (with Category limited to Therapy and Scope limited to Narrow) and Systemic Reviews were used as the search engine to identify relevant publications for this overview. The keywords ‘emollient or moisturizer’ and ‘atopic dermatitis’ were used. The reference lists of some of these publications were reviewed to further identify relevant papers.
Overview
Using the keywords ‘emollient’ and ‘atopic dermatitis’, there were 105 and 36 hits under Clinical Study Categories (with Category limited to Therapy and Scope limited to Narrow) and Systematic Reviews, respectively. Relevant publications are cited in Table 1 and in other sections accordingly.
Table 1.
Selected proprietary moisturizers/emollients and their claimed ingredients.
| Moisturizer | Include | List of ingredients | Clinical efficacy | Biophysical effects | References | |||
|---|---|---|---|---|---|---|---|---|
| P″ | A^ | S* | Claimed active ingredients | Other ingredients/excipients | ||||
| 1. Aqueous cream BP |
|
|
|
|
Mohammed et al. [11] | |||
| 2. Ceradan Cream (Hyphens Pharma Pte Ltd, Singapore) | ✓ |
|
|
|
|
Koh et al. [42] | ||
| 3. Cetaphil Moisturizing Cream (Laboratoires Galderma, Alby-sur-Chéran, France) |
|
|
|
|
Hon et al. [61] | |||
| 4. Cetaphil RESTORADERM Skin Restoring Lotion(Galderma Canada Inc., Thronhill, ON, Canada) | ✓ |
|
|
|
|
Hon et al. [41] | ||
| 5. Canoderm cream 5% (ACO Hud, Upplands Väsby, Sweden) | ✓ |
|
|
|
|
Wirén et al. [62] | ||
| 6. Curel Moisture cream (Kao Corporation, Tokyo, Japan) | ✓ | ✓ |
|
|
|
|
Hon et al. [45] | |
| 7. Curel Moisture cream (Kao Corporation, Tokyo, Japan) | ✓ | ✓ |
|
|
|
|
Seghers et al. [63] | |
| 8. Decubal® original clinic cream (Actavis Pharma, Inc, Parsippany, New Jersey, USA) | ✓ | ✓ |
|
|
|
|
Moss [64] | |
| 9. Ectoin® Dermatitis Cream 7% (Bitop AG, Witten, Germany) | ✓ |
|
|
|
|
Marini et al. [58] | ||
| 10. EpiCeram Skin barrier Emulsion (PuraCap pharmacedutical, Plainfield, NJ, USA) | ✓ |
|
|
|
|
Sugarman et al. [65] | ||
| 11. Eucerin eczema Relief Body Crème (Beiersdorf Inc, Wilton, Connecticut, United States) | ✓ |
|
|
|
|
Weber et al. [66] | ||
| 12. Ezerra cream (Hoe Pharma, Petaling Jaya, Malaysia) | ✓ |
|
|
|
|
Hon et al. [6] | ||
| 13. Intense Hydration & Repair Treatment (Receutics, New York City. NY, USA) | ✓ | ✓ |
|
|
|
|
Draelos et al. [67] | |
| 14. Physiogel A.I. Cream (Stiefel Laboratories Inc, Research Triangle Park, NC, USA) | ✓ |
|
|
|
|
Eberlein et al. [68] | ||
| 15. Suvex Soothe emollient cream (Naturalife Ltd, Rathnew, Ireland) | ✓ |
|
|
|
|
Wakeman et al. [69] | ||
Plant derived claimed-active ingredient.
Animal derived claimed-active ingredient.
Special/synthetic claimed-active ingredients.
CDLQI, children’s dermatology life quality index; DLQI, Dermatology Life Quality Index; IGA, investigator global assessment; POEM, Patient-Oriented Eczema Measure; SCORAD, scoring atopic dermatitis; TEWL, transepidermal water loss.
Selecting an appropriate emollient for a patient is critical, as it is the fundamental treatment for AD. In one survey, aqueous cream was the most commonly used emollient, with petroleum-derived products the next. When comparing aqueous cream with other emollients, aqueous cream users had lower product acceptability and measurably lower skin hydration [8]. Aqueous cream has been known to contain sodium lauryl sulfate (SLS) that can cause skin irritation. Tsang and colleagues reported that chronic use of aqueous cream can cause reduction in stratum corneum thickness and an increase in transepidermal water loss (TEWL) measurements [10]. Treatment with aqueous cream is associated with increased desquamatory and inflammatory protease activity [11]. Aqueous cream BP should not be used as a leave-on emollient in patients with AD [12]. Other than aqueous cream, commercial products available in the market may contain allergens. Common allergens in emollients include fragrances and tocopherol [13]. Eczematous skin may be prone to secondary sensitization and further damage with frequent application of some of the emollients.
Essential oils have recently shown potential therapeutic effects in treating dermatitis or other health conditions. The North American Contact Dermatitis Group tested three fragrance markers and six types of common essential oils, including tea-tree oil, which is often claimed to have anti-inflammatory effects for AD patients. In the study, tea-tree oil was identified to be accounted for 45% of positive reactions among the subjects who were sensitized to essential oils. More than half of the reactions were strong and with definite/probable clinical relevance [14].
Currently, most skin-care products are commonly labeled as ‘dermatologically tested’. Such labeling may be misleading to users. A group conducted a small survey on companies that label their products as ‘dermatologically tested’ and requested testing information from these companies. Of the 25 companies responded, only 4 disclosed the number of subjects tested; 5 said their products had been tested on human skin, but the nature of the tests were not clarified. Thirteen of the companies said a dermatologist was involved in the testing at some point [15]. The investigators also noted that products claiming to be ‘fragrance free’ may also contain a fragrance cross-reactor or botanical ingredient [13].
The advertised prices for emollients for AD can vary. Xu and colleagues showed that best-selling moisturizer products ranged from $0.10 to $9.51 per ounce in the USA. Of the 174 products studied, only 12% were allergen free as described by the North American Contact Dermatitis Group. In addition, products with the claim of ‘dermatologist recommended’ or ‘phthalate free’ had a higher median price per ounce than products without the claim [13].
Various emollient products have been marketed to treat eczema with claim of therapeutic effect. Common ingredients in emollients include petroleum products, glycerin, fatty acids and plant oils. An ideal emollient should contain a combination of occlusive agents to slow down water loss, humectants to increase capacity to withhold moisture and lubricants to reduce friction against skin. As well as the general moisturizing/ water-trapping ingredients, it is common to find other herbal/animal-derived active ingredients added into commercial emollients for supposed advanced beneficial effects. We previously tabulated published data on a number of moisturizers/emollients [6]. Selected proprietary moisturizers/emollients and their claimed ingredients are described in the present paper for comparison (Table 1).
Plant-derived products
Aloe vera
Aloe vera is a stemless, succulent plant with juicy flesh commonly used in the skin-care industry [16]. Other than its moisturizing property, its extracts possess antibacterial and antifungal actions that may aid in preventing secondary infection for AD patients [17,18]. Though this plant has a list of claimed healing properties, to the authors’ best knowledge, there are no control-based trials on AD patients. Most of the clinical trials with aloe vera were done in the field of diabetes and gastrointestinal conditions. The most relevant studies relating aloe vera in AD are two animal studies that were published in 2010 and 2015 [19,20]. Both studies investigated the effect of aloe vera on the immunoglobulin E levels in their AD animal models, though with contrasting results. The group that applied aloe vera extract topically on AD-induced Balb/c mice for 10 days measured a significant reduction in serum IgE levels compared with the placebo control [19]. On the other hand, the group that fed AD-induced NC/Nga mice with aloe vera gel extracts for 6 weeks resulted in significantly lowered serum IL-5 and IL-10 concentration but increased serum IgE levels [20]. Medicinal properties of the aloe plant may vary due to conditional changes. For example, a study has demonstrated freshly prepared aloe vera is more desirable because the gel is sensitive to enzymatic, oxidative and microbial degradation [16]. Also, the percentage of the plant used in the processed emollient may cause variations in its antimicrobial activities [21]. These may all contribute to the non-unifying results among the limited studies.
Coconut oil
Coconut oil is another natural plant-derived product commonly added into emollient formulations [22]. To be accurate, it is necessary to indicate whether it is coconut oil or virgin coconut oil (VCO) that is tested as they have significant differences in properties [23]. By cold-press method, VCO is claimed to be more superior than coconut oil as the active components (such as fatty acids) are not lost during the harsh process [23]. Nonetheless, only a few clinical trials have been reported. Using PubMed search (last retrieval date 23/1/2018), there were only two clinical trials done in the Philippines that investigated the effect of topical VCO on AD patients [24,25]. Both studies showed VCO significantly reduced eczema severity. Some antibacterial results have also been found with VCO in the smaller study involving 26 patients [24]. Further, a microbiological study on agar-diffusion plate confirmed the antibacterial effect of VCO on Staphylococcus aureus. The activity is contributed by the combined effect of medium-chain fatty acids (MCFAs) and monoglycerides, which disrupt the plasma membrane of bacteria [26]. However, another study demonstrated VCO and HVCO did not show their antibacterial activity against several tested bacteria, including Staphylococcus aureus [27]. Further clinical trials are needed before any confirmation on VCO efficacy can be made.
Animal products
Lanolin
Lanolin, also known as wool grease/wool wax, is produced from the sebaceous glands of sheep [28–30]. There are different lanolin derivatives in the market, depending on the method of extraction and modification. Though it is often added into emollients for its occlusion effect, there have been very few studies on its efficacy toward AD patients. Most studies investigated its healing effects toward sore nipples of breast-feeding women [31–33] or problems of allergic contact dermatitis caused by the topical application of lanolin [34,35]. Studies have shown a positive association between atopic dermatitis and lanolin contact allergy [36]. Among the limited emollient trials involving lanolin, a randomized controlled trial with 173 preterm infants showed that a daily treatment with an olive oil/lanolin emollient (30% olive oil, 70% lanolin) showed improved skin condition compared with the vehicle (a water-in-oil emollient cream) [37]. However, this study only investigated its effect toward healthy infants without skin disease. Besides, it was also unsure if the effect of better skin hydration and integrity was contributed by the effect of olive oil or lanolin. In summary, there seems to be substantial evidence that AD patients should avoid daily application of lanolin.
Horse oil
Horse oil is a popular folk ingredient used in the cosmetic industry among Asian countries. It is claimed that horse oil has antibacterial, anti-inflammatory and antipruritic actions on the skin [38]. A Korean study (with English abstract) demonstrated the anti-inflammatory effect of horse oil in reducing erythema and IgE level of DNCB-induced contact hypersensitivity in Balb/c mice [38]. Nonetheless, most studies related to the effects of horse oil are only available in Japanese or Korean with no English translations provided, posing difficulties for dermatologists in the field to evaluate and share the results. It is uncertain if horse oil genuinely contains ingredients from the horse, but many products contain urea.
Special ingredients
Ceramides
Ceramides are lipid molecules found naturally in high concentrations within cell membranes of cells in stratum corneum [9]. Their major function is to maintain the integrity of skin barrier which helps to prevent water loss [39]. Studies have found that the skin of AD patients tend to have lower levels of ceramides [40]. Therefore, the need to restore ceramide levels in AD patients gave rise to the development of ceramide/ceramide-precursor containing emollients [9,41,42]. In fact, ceramide-containing creams have become the attention of dermatological investigators. A review from different clinical studies using emollient-containing ceramide/pseudoceramide found mostly positive feedback though the results may not be exactly coherent. For example, a group reported improved SCORAD (SCORing Atopic Dermatitis) and a significant decrease in TEWL [43], another reported a decrease in TEWL together with an increase in skin hydration [44], and two reported improvements in skin dryness and hydration but no significant improvement in SCORAD or TEWL [41,45]. Pseudoceramides refer to commercially synthesized ingredients that are added in newer moisturizers. They are claimed to possess anti-inflammatory property, improve skin permeability and antimicrobial barrier function [9,45,46].
Natural moisturizing factors
Natural moisturizing factors (NMF) are small molecules which absorb water into the corneocytes thereby hydrating the skin. They are water-soluble filaggrin degradation compound, which are responsible for aggregating keratin filaments to form keratin bundles that maintain the rigid structure of the cells in stratum corneum [5,47,48]. Urea, pyrrolidone carboxylic acid [1,2], glutamic acid and other amino acids are filaggrin-degradation products, collectively referred to as the NMF [49]. These components absorb water from the atmosphere to ensure that the superficial layers of the stratum corneum stay hydrated [50]. The intercellular lipid layer helps prevent the loss of NMF by sealing the outside of each corneocyte [49]. In a small cohort, a test emollient-containing NMF (5% urea), ceramide NP and lactate hydrated the skin to a significantly greater extent and for a longer period of time compared to the control emollient [51]. The results of this small open-label study need to be further confirmed with randomized control trials.
Antimicrobial peptides
Antimicrobial peptides (AMPs), also called host defense peptides, are part of the innate immune response found among all classes of life. These peptides are potent, broad-spectrum antibiotics which demonstrate potential as novel therapeutic agents. AMPs have been demonstrated to kill Gram-negative and Gram-positive bacteria, enveloped viruses, fungi and even transformed cancerous cells [52]. AMPs may also enhance immunity by functioning as immunomodulators. The modes of action by which antimicrobial peptides kill microbes may differ for different bacterial species [53]. Hon et al. investigated an emollient-containing antimicrobial peptide-like activities with claimed multi-actions on barrier repair, antihistaminergic and antimicrobial effects [54]. The investigators found patients who accept the moisturizer have less area affected, disease intensity and severity than the non-accepting counterpart following its usage. However, significant antimicrobial effects are not demonstrated due to the small sample size. Further randomized trials are needed to evaluate the efficacy of the emollient.
Ectoin
Ectoin is an organic osmolyte that has received recent attention. This molecule can be isolated from a wide range of halophilic and halotolerant bacteria that live in extreme conditions [55]. Its function is to provide resistance to the bacteria toward external stresses, mainly dehydration [56] As an osmoprotectant, this molecule is now being studied on human skin with the aim of preventing water loss in dry AD skin through the application of emollient. In vitro studies demonstrated water-retaining ability of ectoin [57]. Clinical trials have also been conducted to test the efficacy of this molecule on patients with AD [58,59].
Review of studies and patient preferences
As reported by van Zuuren and colleagues in 2017, the mean duration of clinical studies on emollients (n=77) was 6.7 weeks and mean age of patients 18.6 years [3,60]. The clinical studies ranged from comparing studied product with vehicle or no treatment. Study participants considered the studied product to be more effective in reducing eczema and symptoms of itch compared to control. In addition, participants applying the studied product reported reduced disease severity and flares compared to placebo, vehicle or no moisturizer as assessed by the investigator. Most moisturizers showed some beneficial effects, namely prolonging time to flare, and reducing the number of flares and amount of topical corticosteroids needed to achieve similar reductions in eczema severity. However, the authors found no evidence that one moisturizer is better than the other [3]. Moisturizers themselves were found to have beneficial effects, and combining moisturizers with active topical treatment produced better results when compared to active topical treatment alone [60].
Hon and colleagues studied the practices and preferences of emollient usage in eczema patients and had the following conclusions: doctors remain the most important source of recommendation. The majority of parents and patients think an ideal moisturizer is a nonfragrant, nonherbal, white or transparent cream that needs only to be used 2 to 3 times per day. Compliance may be enhanced if the recommended moisturizer conforms to the parent’s/patient’s preference [7].
Conclusion
A number of proprietary emollients have undergone trials with clinical data reported in PubMed-indexed journals. Most moisturizers showed some beneficial effects, but there was generally no evidence that one moisturizer is better than the other [3,60]. Choosing an appropriate emollient for AD patients would improve acceptability and adherence for emollient treatment. Physician’s recommendation is the primary consideration for patients when selecting a moisturizer/emollient; therefore, doctors should provide evidence-based information about these emollients.
Footnotes
Disclosure and potential conflicts of interest: The authors declare no conflicts of interest. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors are available for download at: http://www.drugsincontext.com/wp-content/uploads/2018/03/dic.212530-COI.pdf
Correct attribution: Copyright © 2018 Hon KL, Kung JSC, Ng WGG, Leung TF. https://doi.org/10.7573/dic.212530. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0.
Article URL: http://www.drugsincontext.com/emollient-treatment-of-atopic-dermatitis-latest-evidence-and-clinical-considerations
Provenance: invited; externally peer reviewed.
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Peer review comments to author: 16 February 2018
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