THERAPEUTICS FOR THE CLINICIAN The Effect of Ceramide-Containing Skin Care Products on Eczema Resolution Duration Zoe Diana Draelos, MD Eczema is a common dermatologic condition that czema is a common dermatologic condition affects children as well as adults and is related to that is characterized by erythema, desquama- a defective skin barrier, which is most commonly E tion, papulation, lichenification, excoriation, caused by damage to the intercellular lipids from and itching. It affects children as well as adults, improper selection of skin cleansers and moistur- both males and females, and is related to a defec- izers. A new concept in skin care is the incorpo- tive skin barrier, which is most commonly caused ration of ceramides into therapeutic cleansers by damage to the intercellular lipids from improper and moisturizers. Ceramides are important com- selection of skin cleansers and moisturizers. A ponents of the intercellular lipids that are neces- new concept in skin care is the incorporation of sary to link the protein-rich corneocytes into a ceramides into therapeutic cleansers and moistur- waterproof barrier that is capable of protecting izers. Ceramides are important components of the the underlying skin tissues and regulating body intercellular lipids that are necessary to link the homeostasis. This study evaluated the effect of protein-rich corneocytes into a waterproof barrier both a multilamellar vesicular emulsion (MVE) that is capable of protecting the underlying skin ceramide-containing liquid cleanser and mois- tissues and regulating body homeostasis.1,2 With turizing cream plus fluocinonide cream 0.05% the availability of bioidentical synthetic cera- compared with a bar cleanser plus fluocinonide mides 1, 3, and 6, ceramides can be effectively cream 0.05% in the treatment of mild to moder- delivered to the skin through a time-released multi- ate eczema. The addition of an MVE ceramide- lamellar vesicular emulsion (MVE) configuration. containing liquid cleanser and moisturizing cream MVE is a novel emulsion technology. An emul- to a high-potency corticosteroid enhanced the sion is created when water and oil are dissolved to treatment outcome of mild to moderate eczema form one continuous solution. Emulsions can be cre- compared with the use of a bar cleanser and ated either when water is dissolved in oil or when oil high-potency corticosteroid in reducing disease is dissolved in water. If the water is dissolved in oil, duration, time to disease clearance, and symp- the oil is the highest concentration ingredient; if the toms. Thus, skin care product selection can have oil is dissolved in water, the water is the highest con- an important clinical effect on the clearance of centration ingredient. MVE differs from both the mild to moderate eczema. traditional oil-in-water emulsion, whereby the oil Cutis. 2008;81:87-91. is dissolved in water, and the traditional water-in- oil emulsion, whereby the water is dissolved in oil.3 In MVE, there are concentric layers of oil-in-water Accepted for publication November 7, 2007. emulsions, which are referred to as vesicles. The From Dermatology Consulting Services, High Point, North Carolina. vesicles are unfolded when placed in contact with This study was supported by an unrestricted educational grant the skin surface to release ceramides; cholesterol; from Coria Laboratories, Ltd. The author reports no conflict of interest. free fatty acids; phytosphingosine; and other mois- Correspondence: Zoe Diana Draelos, MD, 2444 N Main St, turizing ingredients, such as dimethicone, glyc- High Point, NC 27262 ([email protected]). erin, and hyaluronic acid, onto the skin surface.4 VOLUME 81, JANUARY 2008 87 Therapeutics for the Clinician 90 Treatment group 1 80 Treatment group 2 Treatment group 3 70 % , 60 50 40 30 20 Subjects Assessed as Clear 10 0 �10 0 1 2 3 4 (Baseline) Week Percentage of subjects assessed as clear of disease over the duration of the study. Treatment group 1, fluocinonide cream 0.05% plus mild bar cleanser; treatment group 2, fluocinonide cream 0.05% plus multilamellar vesicular emulsion (MVE) ceramide-containing liquid cleanser; treatment group 3, fluocinonide cream 0.05% plus MVE ceramide- containing liquid cleanser and moisturizing cream. At week 4, P5.155 for treatment group 1 versus treatment group 2; P5.0001 for treatment group 1 versus treatment group 3; and P5.024 for treatment group 2 versus treatment group 3. An MVE ceramide-containing moisturizer should This study was conducted to determine the value provide more rapid barrier repair in eczematous of an MVE ceramide-containing liquid cleanser and skin conditions, yet this concept has never been moisturizing cream in shortening the duration and clinically studied. symptoms of mild to moderate eczema when com- The primary goals in the treatment of eczema bined with a high-potency topical corticosteroid. are the resolution of symptoms, primarily itching, stinging, and burning, and the return of the skin Methods and Materials to a healthy attractive appearance. Both of these The 4-week Concordia Institutional Review Board goals only can be accomplished when the barrier is (Cedar Knolls, New Jersey)–approved study enrolled fully repaired. The dermatologist must determine 60 subjects aged 5 to 80 years with mild to moder- how to shorten the duration of barrier repair in the ate eczema. Subjects underwent a 4-week oral and patient with eczema. Does barrier repair occur in the topical eczema treatment washout period before shortest time when the patient uses a high-potency study entry. At baseline, the investigator (a der- topical corticosteroid and a mild bar cleanser? matologist) performed a brief medical history and Alternatively, is the duration of barrier repair and physical examination of the subjects. Subjects with symptoms shorter when a high-potency topical cor- mild to moderate eczema, defined as the severity ticosteroid is combined with a ceramide-containing of eczema expected to exhibit reasonable clear- liquid cleanser? Is there added benefit to shortening ing with a high-potency topical corticosteroid in the eczema duration and minimizing symptoms when 4 weeks, were enrolled if they met all inclusion and no both a ceramide-containing liquid cleanser and exclusion criteria. Subjects were randomized to 1 of moisturizing cream are added to the high-potency 3 balanced treatment groups of 20 subjects each. topical corticosteroid? Treatment group 1 used fluocinonide cream 0.05% 88 CUTIS® Therapeutics for the Clinician Global Disease Severity by Treatment Group* Treatment P Value Treatment Baseline Week Group 1 vs Group 1 vs Group 2 vs Group Assessment Assessment Difference Group 2 Group 3 Group 3 Week 1 Group 1 3.0 2.6 0.4 .012 .004 .272 Group 2 3.1 1.9 1.2 Group 3 3.0 1.6 1.4 Week 2 Group 1 3.0 2.0 1.0 .442 .013 .063 Group 2 3.1 1.6 1.5 Group 3 3.0 0.9 2.1 Week 4 Group 1 3.0 1.6 1.4 .0443 ,.001 .087 Group 2 3.1 0.9 2.2 Group 3 3.0 0.3 2.7 * Treatment group 1, fluocinonide cream 0.05% plus mild bar cleanser; treatment group 2, fluocinonide cream 0.05% plus multilamellar vesicular emulsion (MVE) ceramide-containing liquid cleanser; treatment group 3, fluocinonide cream 0.05% plus MVE ceramide-containing liquid cleanser and moisturizing cream. twice daily plus a mild bar cleanser as needed. Treat- a 5-point scale (05none, 15minimal, 25mild, ment group 2 used fluocinonide cream 0.05% twice 35moderate, 45severe). A target site was selected daily plus an MVE ceramide-containing liquid cleanser for digital macrophotography. as needed. Treatment group 3 used fluocinonide Statistical analysis was performed on the intergroup cream 0.05% twice daily plus an MVE ceramide- differences from baseline at each visit and the signs containing liquid cleanser as needed and an MVE and symptoms of eczema were tested for significance ceramide-containing moisturizing cream twice daily. (P≤.05) using a nonparametric Kruskal-Wallis test. If Subjects were asked to use only the provided skin a significant difference across treatment groups was care products and medication on the eczematous noted, paired comparisons were analyzed using a 2-tailed areas. A demonstration of the study product applica- nonparametric Mann-Whitney test. Trends in the treat- tion occurred at the research center to ensure that ment groups across the duration of the study were tested subjects properly applied the study medication. Sub- using analysis of variance on rank-transformed data. jects were given instructions and diaries to record the study product application that was appropriate Results for their treatment group. Subjects were required to All 60 subjects completed the 4-week study. No demonstrate the first application of eczema medica- adverse events occurred and no tolerability issues tion before completing the baseline visit. arose with any of the study products as reported by Blinded investigator assessments of global dis- either the investigator or the subjects. The study ease severity and signs and symptoms of eczema was designed to look at the additive benefits of (erythema, desquamation, papulation, lichenifi- fluocinonide cream 0.05% twice daily plus an MVE cation, excoriation, itching) were performed at ceramide-containing liquid cleanser and moisturizing baseline and weeks 1, 2, and 4, and rated on cream. Various data sets were generated. VOLUME 81, JANUARY 2008 89 Therapeutics for the Clinician Incidence and Time to Disease Clearance—The at all time points in the 2 treatment groups using Kaplan-Meier method was used to evaluate the time fluocinonide cream 0.05% plus the MVE ceramide- to disease clearance based on investigator assess- containing liquid cleanser compared with the treat- ments (Figure). The incidence of clearing at week 4 ment group using fluocinonide cream 0.05% plus increased from 15% with fluocinonide cream 0.05% the bar cleanser (P5.05).