Moisturizing Cream Ameliorates Dryness and Desquamation in Participants Not Receiving Topical Psoriasis Treatment

Therapeutics for the Clinician

Zoe Diana Draelos, MD

Psoriasis is a disorder characterized by faster were noted despite the absence of topical pso- than normal skin growth, resulting in a buildup riasis treatment. The investigator assessed that of thickened areas with a scaly appearance. this moisturizer was well-tolerated and appropri- Common sites of involvement include the scalp, ate for use on the damaged skin of participants elbows, knees, and back. Moisturization of these with psoriasis. areas may provide relief by increasing hydration. Cutis. 2008;82:211-216. Accordingly, the use of a moisturizing cream (Cetaphil ® Moisturizing Cream) was studied in participants with mild to moderate plaque psoria- soriasis is a disease of abnormal epidermal prolif- sis (5%–10% body surface area) who either were eration characterized by demarcated erythematic not being treated or had discontinued the use P lesions with silvery scales. The disease typically of all topical psoriasis medications and all other occurs in genetically predisposed individuals follow- moisturizers and remained off of them for the ing exposure to one or more triggering factors such as entire study. The condition of the participants’ skin stress, certain drugs, climate change, infection, skin was objectively monitored for skin barrier function injury, smoking, and alcohol consumption.1 Common through transepidermal water loss (TEWL), skin sites of involvement include the scalp, elbows, knees, hydration through corneometry, and desquamation and back, but lesions or plaques may appear anywhere through the use of sticky tape corneocyte counts on the body. (D-SQUAME ® ). Thirty participants were enrolled. Psoriasis has a substantial impact on the qual- The results of this 4-week study indicate there ity of life of affected individuals, which includes was no further damage to the skin barrier, as no approximately 2% of the worldwide population and significant change in TEWL was seen. Further- nearly 5% of the US population.2 It is a chronic more, skin hydration increased over the course of disease. Although effective treatments providing the study. Desquamation measurements showed relief are available, it often may be short-term, a significant percentage of participants with skin highlighting the need for continued research into improvements from very dry to dry or normal enhancing therapeutic regimens to further aid this (P,.0001 for all time points). All of these effects patient population.2-4 Many dermatologists subscribe to the benefits of a cleansing and moisturizing routine in conjunction Accepted for publication May 9, 2008. with therapy for many dermatologic conditions. From Dermatology Consulting Services, High Point, Accordingly, they generally have samples from a North Carolina. variety of skin care companies claiming to have This study was supported by a grant from Galderma Laboratories, cleansers and moisturizers that increase hydration LP. Dr. Draelos is a consultant and researcher for Galderma Laboratories, LP. and therefore help ameliorate the symptoms asso- Correspondence: Lori A. Johnson, PhD, 14501 N Freeway, ciated with many dermatologic conditions. It is Fort Worth, TX 76177 ([email protected]). of interest that these products typically are tested

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on the skin of healthy volunteers and not on skin affected by the condition for which the products Participant Demographics are being recommended. Therefore, a study was conducted to test a moisturizing cream on the Participants affected skin of participants with plaque psoriasis Characteristic (N530) in the absence of topical psoriasis treatment. Skin barrier function, skin hydration, and desquamation Sex, n (%) each were objectively measured, and a tolerability Male 14 (47) analysis was carried out. The participants also were monitored for adverse events. A survey also was Female 16 (53) conducted to capture each participant’s perspective on the use of this moisturizer. Age, ya Mean 53 Materials and Methods The objective of this study was to evaluate the use Median 59 of a moisturizing cream (Cetaphil® Moisturizing Cream)(containing purified water, polyglycerylmeth- Range 24–81 acrylate and propylene glycol, petrolatum, dicaprylyl Race, n (%) ether, PEG [polyethylene glycol]-5 glyceryl stearate, glycerin, dimethicone and dimethiconol, cetyl alco- White 29 (97) hol, prunus amygdalus dulcis [sweet almond] oil, acrylates/C10-30 alkyl acrylate crosspolymer, Hispanic 1 (3) tocopheryl acetate, phenoxyethanol, benzyl alcohol, Fitzpatrick skin type, n (%) disodium EDTA, sodium hydroxide, lactic acid) on the compromised skin of participants with plaque I 2 (7) psoriasis covering 5% to 10% of the body. Assess- ments included an analysis of skin barrier function, II 21 (70) skin hydration, and desquamation, as well as the par- III 5 (17) ticipants’ perspective and regimen compliance. The study design called for 30 participants aged IV 2 (7) 18 to 70 years with plaque psoriasis defined as slight plaque thickening with definite elevation, Body coverage, % fine scales partially or mostly covering lesions, and Mean 7.6 any erythema up to a moderate rating (definite red coloration). Pregnant women were excluded from Median 8.0 enrollment. Eligible participants included those who either were not being treated or had discontin- Range 5.0–10.0 ued the use of all topical psoriasis medications and Duration of disease, y all other moisturizers and remained off of them for the entire study. They were instructed to use the Mean 9.5 moisturizing cream twice daily (once in the morn- ing and once in the evening). Assessments were Median 8.5 performed at baseline and weeks 1, 2, and 4, as Range 1.0–30.0 described below. Skin barrier function was objectively determined Discontinued, n (%) through transepidermal water loss (TEWL) using the DermaLab® TEWL probe. This technique works For medical reason 0 (0) by using a probe containing 2 humidity meters Participant request 1 (3) at a known distance from the skin. As the water vapor passes by the 2 humidity meters, the level Lost to follow-up 1 (3) is measured and the difference between the water a content at the 2 different time points is determined. Two participants, aged 71 and 81 years, exceeded the age requirement but were granted exceptions by the investigator This difference is, in effect, the TEWL. Increased and enrolled in the study. TEWL is expected when the skin barrier is damaged and water flows from the moist skin to the

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21.5 20.6 19.9 19.9 20

15 Mean TEWL 10

0 Baseline Week 1 Week 2 Week 4 Visits

Figure 1. Mean value from 2 independent readings for transepidermal water loss (TEWL) from the psoriasis lesion objectively determined using the DermaLab® TEWL probe. No significant change was seen at weeks 1, 2, or 4 compared with baseline.

lower-humidity air. A decrease in TEWL would be Desquamation was objectively measured through indicative of improved barrier function, and no change sticky tape corneocyte counts using D-SQUAME® would be indicative of preserved barrier function. A skin sampling discs. In this study, the adhesive linear mixed-effects analysis of variance was used to discs were applied under standardized pressure onto compare mean TEWL at each week with baseline the surface of the skin, harvesting the cells from (a5.05). The analysis controlled for sex, age, and race, the most superficial layers of the skin. The discs and was not adjusted for multiple comparisons. then were placed on a black background support Skin hydration was objectively measured through and homogeneously illuminated. Determination of corneometry using DermaLab technology. In this the number of dead cells adhering to the disc was study, the corneometry was measured using a pin probe. analyzed by a trained evaluator using a standardized The probe is activated by depressing the pins, which scale (scored from 1–3). The scale was translated produces a low-level electric current that is conducted into 3 skin categories: very dry, dry, normal. A through the skin by the water contained within the generalized estimating equation model for ordinal skin. The sensing pins determine how much elec- data was used to compare scores at each week with tric current has been received. This measure of skin baseline (a5.05). The model controlled for sex, electric conductivity is an indirect measure of skin age, and race. The analysis was not adjusted for water content. Thus, higher corneometry values are multiple comparisons. indicative of improved skin hydration. A linear mixed- Participants were asked to rate 4 attributes of the effects analysis of variance was used to compare mean moisturizer on a scale of 1 to 10, with 10 represent- corneometry at each week with baseline (a5.05). The ing the best/most positive rating for the attribute analysis controlled for sex, age, and race, and was not and 1 the worst/least positive rating. The 4 queried adjusted for multiple comparisons. attributes were ease of use, perceived effectiveness,

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250 * 235.8

200 † 186.4

157.4 150

126.1

100 Mean Corneometry

0 Baseline Week 1 Week 2 Week 4 Visits

Figure 2. Mean value from 2 independent readings for skin hydration from the psoriasis lesion objectively determined using DermaLab® technology. P values represent values measured at weeks 1 and 2 compared with baseline. Asterisk indicates P,.0001; dagger, P,.05. satisfaction, and plans for future use. The results of Transepidermal water loss was objectively mea- this survey were summarized descriptively. sured to determine the effects of twice-daily moisturizing with the moisturizing cream on skin barrier Results function. Although there were minimal changes Thirty participants with plaque psoriasis were enrolled in the values reported, there was no significant and began moisturizing twice daily with the moisturiz- change in TEWL over the course of the study, ing cream. One participant withdrew from the study by indicating that the skin barrier was not further request because of absence from visits at weeks 1 and 4, damaged. Maintaining the condition of the skin and another participant was lost to follow-up, leaving barrier was particularly unexpected because of the 28 evaluable participants. There also were 2 protocol lack of topical psoriasis treatment, which would violations consisting of 2 participants who exceeded expectedly help to reverse skin barrier impairment the age requirement. These 2 participants, aged 71 and (Figure 1). 81 years, were granted exceptions by the investigator. Skin hydration was objectively measured to They were enrolled in the study and included in the assess the effects of twice-daily moisturizing with analysis. Demographic information on all participants the moisturizing cream on the level of hydration in is summarized in the Table. Most participants were the skin. It was expected that skin hydration levels female (53%; 16/30), were white (97%; 29/30), and would decrease over the course of the study, as these had Fitzpatrick skin type II (70%; 21/30). Participants participants were not receiving any topical treat- ranged in age from 24 to 81 years (mean, 53 years). ment for their psoriasis. On the contrary, skin hydra- The mean plaque coverage was 7.6% of the body and tion improved over the course of the study compared the mean disease duration was 9.5 years. with baseline. This improvement was significant at

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Very dry Dry Normal

100 * * * 3.6 10.3 16.0

80 50.0 73.3 48.3 % 60 44.0

Participants, Participants, 40

20 40.0 41.4 46.4 16.7

10.0 0 Baseline Week 1 Week 2 Week 4 Visits

Figure 3. Distribution of participants among 3 skin categories (very dry, dry, normal) describing the severity of desquamation using D-SQUAME® skin sampling discs. P values represent comparison with baseline. Asterisk indicates P,.0001. week 1 (P,.0001) and week 2 (P,.05) but was not on a scale of 1 (worst) to 10 (best). When asked significant at week 4 (Figure 2). about ease of use, 79% (23/29) of participants gave Desquamation was objectively measured using the moisturizing cream a score of 10. When asked D-SQUAME skin sampling discs. The distribution about perceived improvement, 62% (18/29) of the of participants among 3 skin categories (very dry, participants rated the cream 7 or better. More than dry, normal) significantly improved over the course half (55% [16/29]) of the participants scored their of the study, with 73.3% (22/30) of participants satisfaction with the cream as 8 or better. Finally, having very dry skin at baseline, 16.0% (4/25) at 62% (18/29) of participants scored their likeliness week 1, 10.3% (3/29) at week 2, and only 3.6% (1/28) of future use as 10. The therapeutic regimen com- at the end of the study (week 4), with proportion- pliance rate for this study was reported as 99.6%. ately more participants in the other 2 categories (dry, In addition, the investigator assessed the moistur- normal) at each time point after baseline (P,.0001 izing cream as well-tolerated for use in participants for all time points)(Figure 3). Statistically dichoto- with psoriasis. mized analyses also revealed that significantly fewer participants had very dry skin at each time point Comment compared with baseline (P,.001 for each time point) Psoriasis is a chronic disorder characterized by scaling and significantly more participants had normal skin and inflammation of the skin. Scaling occurs because at each time point compared with baseline (week 1, the cells of the outer skin layer are reproducing faster P,.05; weeks 2 and 4, P,.01)(Figure 3). than normal and thus piling up at the skin’s surface. Participants were asked to complete a survey In the most common form, plaque psoriasis (psoria- grading their thoughts about the moisturizing cream sis vulgaris),5 the skin lesions have a reddened base

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covered by silvery scales. These plaques damage the References skin barrier and consequently allow release of mois- 1. Ockenfels HM. Trigger factors for psoriasis [in German]. ture from the skin.6 Although moisturizers cannot be Hautarzt. 2003;54:215-223. used as treatment for psoriasis, they may provide some 2. Christophers E. Psoriasis—epidemiology and clinical relief from the symptoms of skin dryness by increas- spectrum. Clin Exp Dermatol. 2001;26:314-320. ing skin hydration and restoring the integrity of the 3. van de Kerkhof PC, de Hoop D, de Korte J, et al. Patient stratum corneum of the affected areas.7-10 To identify compliance and disease management in the treatment an etiologic factor of this extreme dryness, prior stud- of psoriasis in the Netherlands. Dermatology. 2000;200: ies have extensively examined the hydration and 292-298. water-retention capacity of the stratum corneum in 4. Krueger G, Koo J, Lebwohl M, et al. The impact of pso- participants with psoriasis.11-13 It has been reported riasis on quality of life: results of a 1998 National Psoriasis that impaired barrier function and increased TEWL Foundation patient-membership survey. Arch Dermatol. corresponded with dry skin conditions. In addition, a 2001;137:280-284. decrease in water-binding properties and a reduction 5. Nast A, Kopp I, Augustin M, et al. German in skin surface lipids, specifically levels of ceramides, evidence-based guidelines for the treatment of psoriasis contributed to the dryness and scaliness symptoms vulgaris (short version). Arch Dermatol Res. 2007;299: of psoriasis.6,10 Furthermore, it has been reported 111-138. that the structural organization of these lipids in the 6. Bouwstra JA, Ponec M. The skin barrier in healthy stratum corneum of the affected skin has been altered and diseased state. Biochim Biophys Acta. 2006;1758: in comparison to healthy skin.6 Clinical studies have 2080-2095. shown that use of an appropriate moisturizer can alle- 7. Lodén M. The clinical benefit of moisturizers. J Eur Acad viate some of these skin deficiencies in participants Dermatol Venereol. 2005;19:672-688. with healthy skin.7,10 Thus, this study examined the 8. Held E, Agner T. Effect of moisturizers on skin susceptibil- benefits of a moisturizer on the affected skin of par- ity to irritants. Acta Derm Venereol. 2001;81:104-107. ticipants with psoriasis. 9. Held E, Sveinsdóttir S, Agner T. Effect of long-term use of It was observed that twice-daily application moisturizer on skin hydration, barrier function and suscep- of the moisturizing cream maintained the func- tibility to irritants. Acta Derm Venereol. 1999;79:49-51. tion of the skin barrier despite the lack of topical 10. Lebwohl M, Herrmann LG. Impaired skin barrier function treatment in participants with plaque psoriasis in a in dermatologic disease and repair with moisturization. 4-week period. In addition, twice-daily moisturizing Cutis. 2005;76(suppl 6):7-12. significantly increased skin hydration at weeks 1 11. Berardesca E, Fideli D, Borroni G, et al. In vivo hydra- and 2 (P,.0001 and P,.05, respectively). Des- tion and water-retention capacity of stratum corneum in quamation, measured by the change in distribution clinically uninvolved skin in atopic and psoriatic patients. of D-SQUAME scores, also significantly improved Acta Derm Venereol. 1990;70:400-404. with the use of the moisturizing cream during this 12. Kim SD, Huh CH, Seo KI, et al. Evaluation of skin 4-week study (P,.0001 for all time points). More- surface hydration in Korean psoriasis patients: a possible over, according to the investigator’s assessments, this factor influencing psoriasis. Clin Exp Dermatol. 2002;27: moisturizer was well-tolerated and appropriate for use 147-152. on the damaged skin of participants with psoriasis. 13. Rim JH, Jo SJ, Park JY, et al. Electrical measurement of Collectively, these results may indicate the impor- moisturizing effect on skin hydration and barrier func- tance of a moisturizer as a component in a psoriasis tion in psoriasis patients. Clin Exp Dermatol. 2005;30: skin care regimen to help alleviate skin dryness. 409-413.

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