Drug Therapy Topics

The Use of as an Integral Component of Topical Therapy for Rosacea: Clinical Results Based on the Assessment of Skin Characteristics Study

James Q. Del Rosso, DO

Skin care regimens have been recommended in symptoms of rosacea.1-7 Several studies have dem- conjunction with topical medications for the treat- onstrated the effectiveness of properly chosen skin ment of rosacea. Specifically, a mild cleanser cleansers, proper cleansing technique, and and a moisturizer can help relieve symptoms and use in minimizing signs and symptoms of rosacea such maintain skin barrier integrity. The Assessment as erythema, dryness, scaling, stinging, burning, and of Skin Characteristics Study, a multicenter open- pruritus.1,5,6,8 Additionally, the use of a gentle syn- label study (N5102), compared the use of a thetic detergent (syndet) skin cleanser was shown to specified skin care regimen with or without the improve signs and symptoms of rosacea as compared moisturizer component. Participants used a facial to a soap-based cleanser in participants maintained cleanser immediately before application of aze- on topical metronidazole.4 laic acid (AzA) gel 15% twice daily to both sides Dryness of skin and scaling are not infrequent of the face and then applied the provided mois- in patients with rosacea, and the utility of mois- turizer to the right side of the face only. Scores turizers in these patients is relevant.7 However, for severity and duration of stinging, burning, there is evidence that moisturizer use could play tingling, and itching were recorded in the morn- an integral adjunctive role in the topical manage- ing and evening for 7 days. Cumulative symptom ment of rosacea. In one controlled study, use of a scores (CSSs) decreased on the right side of the niacinamide-containing moisturizer not only face with facial moisturizer applied. improved facial skin hydration in participants with Cutis. 2009;84:72-76. rosacea, as measured by transepidermal water loss, corneometry, and chemical probe measurements, but also was associated with reductions in erythema and oth clinical experience and recent research inflammatory lesions as well as dryness and scaling.8 have supported the importance of an appropri- The hyperirritability of facial skin in rosacea; B ate skin care regimen in mitigating signs and its susceptibility to external stimuli, including skin care products; and the presence of subjective symp- toms such as stinging, burning, tingling, and - From Valley Hospital Medical Center, Las Vegas, Nevada. ing are indicative of inherent sensitive skin.9 Skin Completion of the Assessment of Skin Characteristics Study was supported by Intendis, Inc. Dr. Del Rosso is a consultant, researcher, sensitivity correlates with impaired epidermal bar- 10 and speaker for Allergan, Inc; Coria Laboratories, Ltd; Galderma rier function. Increased transepidermal water loss, Laboratories, LP; Graceway Pharmaceuticals, LLC; Intendis, Inc; reflective of epidermal barrier dysfunction, has Medicis Pharmaceutical Corporation; Obagi Medical Products, Inc; been demonstrated predominantly in the central Onset Therapeutics; OrthoNeutrogena; Quinnova Pharmaceuticals, facial region of patients with both erythematotel- Inc; Ranbaxy Laboratories Ltd; SkinMedica, Inc; Stiefel Laboratories, Inc; Triax Pharmaceuticals, LLC; Unilever; and Warner Chilcott. angiectatic rosacea (subtype 1) and papulopustular 11 Correspondence not available. rosacea (subtype 2).

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What is the Assessment of Skin of stinging, burning, tingling, and itching as Characteristics Study? reported by the participant; and participant age, The Assessment of Skin Characteristics Study was sex, race, skin type, and the facial cleanser and a multicenter open-label study of participants with moisturizer used. mild to moderate papulopustular rosacea (subtype 2) who used a specified skin care regimen including a designated facial cleanser and moisturizer in conjunc- What was the procedure used for application of tion with a topical medication, azelaic acid (AzA) topical medication and skin care products? gel 15%, twice daily. The aim of the study was to On the first study day, investigators provided par- assess the effect of this regimen on symptoms of ticipants with AzA gel 15%, a designated facial stinging, burning, tingling, and itching in rosacea, cleanser (CeraVe™ Hydrating Cleanser or Cetaphil® particularly to see if the regular application of a facial Gentle Skin Cleanser), and a designated facial mois- moisturizer provided any measurable improvement turizer (CeraVe Moisturizing Cream or Cetaphil in symptom relief as compared to the same regimen Moisturizing Cream), and instructed them to adhere without moisturizer. Preliminary findings based on to the following procedure twice daily in the morning the first 24 participants were previously outlined.1 and evening for 7 days: (1) Wash the face gently with The final results (N5102) are discussed here. the provided skin cleanser only. (2) After gently dry- ing the face, evenly apply AzA gel 15% to the entire face. (3) Apply the provided moisturizer to the right What methods were used in the evaluation of side of the face only. (4) Score sensations of sting- skin characteristics? ing, burning, tingling, and itching on the left and The target number for recruitment into the study was right sides of the face for severity (05none; 15mild; approximately 100 individuals who could participate 25moderate; 35severe) and duration (in minutes), with minimal disruption to their usual routine and and record the information in a participant diary in regular visits to their dermatologist (study investiga- the am and pm. tor). Participants were provided with the designated topical prescription medication and specific skin care products as well as instructions on the proper method How were data reported and analyzed? of skin cleansing and application of the topical medi- Separate scores for stinging, burning, tingling, and cation and facial moisturizer. itching were averaged at each measurement point to A split-face design was employed. After washing provide a cumulative symptom score (CSS). Because the entire face with the designated facial cleanser these sensations are highly subjective and partici- provided by the investigator, participants applied pants might categorize them differently, the CSS AzA gel 15% to both sides of the face and then served as an overall measure of facial discomfort. To applied the provided moisturizer to the right side of reveal trends in symptom severity, mean CSSs for the face only. Participants recorded scores for sever- each side of the face were calculated for am and pm ity and occurrence of stinging, burning, tingling, on all 7 study days for all participants. The statistical and itching on each side of the face. analysis, however, was not done on the mean CSS Participants were recruited by 4 dermatologists but by pairwise comparison of individual CSSs using at different ambulatory practices in a Wilcoxon signed rank test. These comparisons were the United States. The study included participants between (1) baseline (am of day 1) and end of study 18 years of age and older with mild to moderate (pm of day 7) for each side of the face for each partici- papulopustular rosacea (subtype 2) and facial ery- pant, and (2) left and right side of the face for each thema as determined by the investigators. Exclusion participant at end of study. criteria included treatment with topical agents in Symptom durations were analyzed both by paired the preceding 2 weeks, oral agents (antibiotics, anti- Student t test and Wilcoxon signed rank test in case inflammatory dose doxycycline) in the preceding there were extreme outliers. When more than one 4 weeks, or isotretinoin in the preceding 6 months; symptom occurred at the same time on the same pregnancy; breastfeeding; concomitant skin condi- side of the face and durations recorded for the dif- tions; underlying medical conditions; or treatments ferent symptoms were different, these durations that the investigator determined might interfere were averaged. with study results. Mean CSSs and durations were calculated on During the initial interview, investigators the basis of all available participant diary entries for recorded baseline scoring on erythema and inflam- each measurement point. Pairwise comparisons were matory lesions; baseline severity and frequency done for all available pairs.

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Statistical significance was defined as P≤.05 (2-tailed test). Baseline Characteristics (N5102)

What were the skin characteristics captured at Characteristic Participants, n baseline that were associated with the presence Age, ya of papulopustular rosacea? 20–39 29 Baseline characteristics of the participant population are shown in the Table and baseline symptoms are 40–59 52 shown in Figure 1. .60 21 Overall, 78 of 102 participants enrolled in the study reported regularly experiencing symptoms of Sex stinging, burning, tingling, and/or itching before Female 85 the study began. Itching was the symptom expe- Male 17 rienced by the greatest percentage of participants (53% [54/102]) and was described as severe by Race 13% (7/54) of those participants who experienced White 92 it. The symptom that occurred most frequently among those participants who experienced it was Black 2 burning. Burning was noted as a daily occurrence Asian 3 by 11 of 45 participants (24%) who reported Other 5 this symptom and was the symptom most often described as either moderate or severe as noted Skin type by 42% (19/45) of those participants with this Dry 21 symptom. Tingling was experienced by the fewest participants and also was experienced with the Oily 27 least frequency, with only 5 participants (13%) Normal 34 reporting that they experienced tingling every day. It also was the symptom most often described Other/combination 20 as mild as noted by 82% (31/38) of those partici- Erythema pants who experienced it. Light red or pink 32 Red 59 What changes in skin characteristics were noted Beet red 10 over the course of the evaluation? Ten participants did not return diaries after the N/A 1 study and an additional 14 diaries had incomplete Inflammatory lesions, n or missing data. Mean CSS for the 2 regimens at 1–10 54 am and pm of the 7 study days is shown in Figure 2. Starting with similar scores at baseline, there was 11–20 37 a reduction for both regimens over the course of .20 10 the study. There was a greater overall reduction for the regimen with moisturizer applied to the right N/A 1 side of the face compared to the left side without Abbreviation: N/A, not available. moisturizer. Comparing end of study values of the aThe age range was 20–80 years. CSS to baseline for each treatment, the reduc- tion in CSS proved significant for the regimen with moisturizer (P5.008) but not for the regimen without moisturizer. End of study CSSs also were significantly lower with moisturizer versus without recorded on the left side of the face by 1 partici- moisturizer (P5.015). pant. These differences were not significant under There were marked differences in mean dura- either parametric or nonparametric testing. From tion of symptoms for the 2 regimens during the first the second study day through the end of the study, study day, mostly attributable to a single outlier, mean duration of symptoms were in the range of 7 to which was symptom duration of more than an hour 9 minutes for both regimens.

74 CUTIS® Drug Therapy Topics

60

54

50 7 45 45 n 2 3 Severe 40 38 11 1 Moderate 14 16 6 Mild 30

20 36

Participants With Symptom, 31 29 26 10

0 Stinging Burning Tingling Itching

Figure 1. Baseline symptoms of stinging, burning, tingling, and itching (N5102). Data are missing for one participant for burning and tingling.

0.35

0.30

0.25 e 0.20 Without moisturizer With moisturizer 0.15 Mean Scor

0.10

0.05

0 AM PM AM PM AM PM AM PM AM PM AM PM AM PM 1 2 3 4 5 6 7

Study Day

Figure 2. Mean cumulative symptom scores recorded over 7 study days at am and pm for participants treated with aze- laic acid gel 15% and a facial cleanser, with or without a moisturizer.

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What can be concluded from the results of literature review. J Clin Aesthet Dermatol. 2008;1: this evaluation? 20-25. The study appears to confirm that the inclusion of a 2. Draelos ZD. Facial hygiene and comprehensive manage- moisturizer in a skin care regimen used in conjunc- ment of rosacea. Cutis. 2004;73:183-187. tion with a topical rosacea medication, AzA gel 15%, 3. Del Rosso JQ. Adjunctive skin care in the man- improves rosacea symptom relief as compared with agement of rosacea: cleansers, moisturizers, and the same regimen without moisturizer. Starting photoprotectants. Cutis. 2005;75(suppl 3):17-21, with equivalent baseline values, CSS in the regimen 33-36. with moisturizer decreased markedly, while CSS in 4. Subramanyan K. Role of mild cleansing in the manage- the regimen without moisturizer did not, and the end ment of patient skin. Dermatol Ther. 2004;17(suppl 1): of study CSS was significantly lower in the regimen 26-34. with moisturizer (P5.015). 5. Draelos ZD. Effect of Cetaphil Gentle Skin Cleanser Given the characteristic presence of sensitive skin on the skin barrier of patients with rosacea. Cutis. symptoms in patients with rosacea, which appears to 2006;77(suppl 4):27-33. correlate at least partially with impaired epidermal 6. Bikowski J. The use of cleansers as therapeutic con- barrier function, and the role of skin hydration in comitants in various dermatologic disorders. Cutis. maintaining the integrity of the epidermal barrier, 2001;68(suppl 5):12-19. the reduction in subjective signs and symptoms of 7. National Rosacea Society. Dry skin found common facial skin irritation observed in this evaluation are among rosacea sufferers. Rosacea Review. Summer 1996. attributed to the improvement in stratum corneum http://www.rosacea.org/rr/1996/summer/article_3.html. integrity after moisturizer use.10,12 Accessed October 1, 2008. It can be concluded based on this evaluation and 8. Draelos ZD, Ertel K, Berge C. Niacinamide- others that the overall level of facial discomfort, containing facial moisturizer improves skin barrier characterized as stinging, burning, tingling, and/or and benefits subjects with rosacea. Cutis. 2005;76: itching, is appreciably reduced by the addition of 135-141. a moisturizer to the topical skin care regimen in 9. Kligman AM. Human models for characterizing patients with rosacea.1-6,8 “sensitive skin.” Cosmet Dermatol. March 2001;14: 15-19. Acknowledgments—Special thanks to other study 10. Muizzuddin N, Marenus KD, Maes DH. Factors defining investigators: Michelle Barton, NP, Brentwood, sensitive skin and its treatment. Am J Contact Dermat. Tennessee; Eric Baum, MD, Gadsden, Alabama; and 1998;9:170-175. Steve Hawkes, PA-C, Henderson, Nevada. 11. Dirschka T, Szliska C, Jackowski J, et al. Impaired skin barrier and atopic diathesis in perioral . J Dtsch References Dermatol Ges. 2003;1:199-203. 1. Del Rosso JQ, Baum EW. Comprehensive medi- 12. Draelos ZD. Therapeutic moisturizers. Dermatol Clin. cal management of rosacea: interim study report and 2000;18:597-607.

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