- Email: [email protected]
Pseudoaneurysm of Superficial Temporal Artery After Frontal Scalp Laceration Debridement
Australasian Journal of Dermatology (2019) , –
doi: 10.1111/ajd.13153
ORIGINAL RESEARCH
Skin benefits of moisturising body wash formulas for children with atopic dermatitis: A randomised controlled clinical study in China Zigang Xu1 | Xiaoyan Liu2 | Yueqing Niu3 | Chunping Shen1 | Kate Heminger4 | Laurie 4 Moulton | Amy Yu3 | Tina Allen4 | Lesheng Zhang3 | Feng Yue3 | Jiquan Liu5 | Ying Xu5 | Helen Zhao5 | Lijuan Li4 | Tom Cambron4 | Jian Xu6 | Ed Smith4 | Karl Wei4 1
Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, 2Department of Dermatology, Capital Institute of Pediatrics, 3Procter & Gamble Beijing Innovation Center, Beijing, China, 4 Procter & Gamble Mason Business Center, Mason, Ohio, USA, 5Procter & Gamble Singapore Innovation Center, Singapore City, Singapore, and 6Qingdao Institute of BioEnergy and BioProcess Technology, Chinese Academy of Sciences, Qingdao, China
ABSTRACT Background: It acknowledged that skin care is an important part of atopic dermatitis therapy. However, clinical evidences are limited for the best bathing practices, especially the skin health performance of cleansing products on children’s atopic dermatitis skin.
Correspondence: Karl Wei, Procter & Gamble Mason Business Center, Mason, OH 45040, USA. Email: [email protected] Zigang Xu, MD. Xiaoyan Liu, MD. Yueqing Niu, MD. Chunping Shen, MD. Kate Heminger, PhD. Laurie Moulton, MS. Amy Yu, BS. Tina Allen, BS. Lesheng Zhang, PhD. Feng Yue, MS. Jiquan Liu, PhD. Ying Xu, PhD. Helen Zhao, PhD. Lijuan Li, PhD. Tom Cambron, PhD. Jian Xu, PhD. Ed Smith, BS. Karl Wei, PhD. Consent for Publication from All Authors: Yes. Funding information: This study was supported by a research grant from The Procter &Gamble Company. Conflict of interest: Yueqing Niu, Kate Heminger, Laurie Moulton, Amy Yu, Tina Allen, Lesheng Zhang, Feng Yue, Jiquan Liu, Helen Zhao, Lijuan Li, Tom Cambron, Ed Smith and Karl Wei contributed to and/or conducted this study while employed by The Procter & Gamble Company. The other authors declare that they have no conflict of interest. Study ethics: This study protocol complied with the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the institutional review committee of Beijing Children’s Hospital and conducted per ICH guidelines for Good Clinical Practice. Written informed consent was obtained from the parent/ legal guardian of each subject and verbal assent from each subject. No recognisable photographs were collected from this study. Submitted 28 January 2019; accepted 5 August 2019. © 2019 The Australasian College of Dermatologists
Methods: A randomised controlled clinical study was conducted in China among 4- to 18-year-old children with mild-to-moderate atopic dermatitis to evaluate the skin health effect of three cleansing systems (a mild synthetic bar, an ultra-mild body wash with lipids, and an ultra-mild body wash with lipids and zinc pyrithione) by measuring SCORing of Atopic Dermatitis (SCORAD), consumption of topical corticosteroid and the characteristics of microbiome. Results: Increased Staphylococcus aureus abundance and decreased microbial diversity were observed in atopic dermatitis lesion sites compared with healthy control sites. After 4 weeks of treatment, all three treatments showed clinically important improvement from baseline in SCORAD. Fourweek corticosteroid consumption was significantly lower for the two body wash groups than the bar group. A significant decrease in S. aureus abundance and increase in microbial diversity were observed in the lesion sites for the two body wash formulas, while the microbial diversity was statistically insignificant for the mild cleansing bar group. However, there were no incremental benefits provided by the body wash formulas based on the assessment of SCORAD. Conclusions: These results demonstrated the safety and efficacy of using the investigational body wash formulas with lipids in reducing the needs for corticosteroid and improving the healthy composition of skin microbiome vs. the mild synthetic bar soap. Key words: atopic dermatitis, body wash, microbiomes, skin health.
Z Xu et al.
2
INTRODUCTION Maintaining and enhancing epidermal barrier function plays a critical role in atopic dermatitis (AD) treatment. Use of moisturisers is considered as an effective way to prevent transepidermal water loss (TEWL), prevent flareups and reduce the need for pharmacologic treatment. Bathing for AD patients can be double-edged: it removes crusts, irritants, allergens and bacterial plaques, but at the same time poses further challenges to epidermal barrier integrity.1 The development of moisturising body wash products is one of the more significant changes to affect the personal cleansing market in recent years.2 A key factor contributing to the popularity of these products is that the advanced body wash technologies can be designed to deliver better skin care benefits than regular cleansing body washes or mild bat soaps. The aim of study was to evaluate the health effect of three cleansing systems, a mild synthetic bar, an UltraMild Body Wash with Lipids, and an ultra-mild body wash with lipids and zinc pyrithione (ZPT) among children with mild-to-moderate AD conditions.
MATERIALS AND METHODS Study design This was a randomised, single-blind, parallel group, in home use study consisting of 1-week pre-conditioning phase, 4-week treatment phase and 2-week follow-up phase, conducted over the period May to July 2015. This study protocol was approved by the institutional review committee of Beijing Children’s Hospital and conducted according to ICH guidelines for Good Clinical Practice. Written informed consent was obtained from the parent/legal guardian of each subject and verbal assent from each subject prior to screening. There is no conflict of interest with the products used.
Subject Subjects were recruited from the Outpatient Department of Pediatric Dermatology, Beijing Children’s Hospital and Capital Institute of Pediatrics. The AD group were 4–18 years of age (inclusive), diagnosed as mild-to-moderate AD according to the Physician’s Global Assessment (PGA = 2 or 3) with active lesions involving 5% to 30% of the body surface. Healthy controls were age- and gender-matched to the AD group, with no history or current presentation of AD.
Intervention After baseline visit, the healthy control subjects were discharged from the study, and the AD subjects were randomised into three treatment groups (a mild synthetic bar, an ultra-mild body wash with lipids, and an ultra-mild body wash with lipids and ZPT) and required to wash once daily with the assigned investigational product. The key © 2019 The Australasian College of Dermatologists
ingredients of the mild synthetic bar are sodium lauryl isethionate, paraffin, sodium cocoglyceryl ether sulphonate, glycerine, water etc. The key ingredients of the ultramild body wash with lipids are water, petrolatum, sodium trideceth sulphate, sodium chloride, cocamidropropyl betaine, trideceth-3, fragrance, guar hydroxypropyltrimonium chloride, sodium benzoate, xanthan gum, glyceryl oleate etc. The key ingredients of the ultra-mild body wash with lipids and ZPT are water, petrolatum, sodium trideceth sulphate, sodium chloride, cocamidropropyl betaine, trideceth-3, fragrance, guar hydroxypropyltrimonium chloride, sodium benzoate, xanthan gum, glyceryl oleate, zinc pyrithione etc. Additionally, all subjects were asked to apply 0.1% hydrocortisone butyrate cream to their AD lesion sites once per day until the lesion was gone using the ‘the fingertip unit method’, in place of their previous topical medication. Upon completion of the 4-week treatment phase, subjects discontinued the use of topical corticosteroid for the following 2-week follow-up phase. No other products or medications were allowed except those provided by this study.
Measurement and sample collection During each visit, subjects acclimated in a controlled temperature and controlled humidity room for at least 30 min prior to sample collection. A trained dermatologist, blinded to the three treatment groups, used the SCORing of Atopic Dermatitis (SCORAD) to evaluate the severity of AD. The amount of investigational products and topical corticosteroid used was also collected. Swab samples were collected by applying each swab onto a 10 cm2 skin site in both horizontal and vertical directions for total 50 times. The sampling procedures were performed by trained technicians, and were stored in 80°C freezer until analysed for biomarker and microbiome.3
Statistical analysis A mixed model was used with subject (random effect) and skin type (fixed effect) for comparison of lesion, non-lesion and the skin of healthy controls at baseline. For comparison of 4-week usage of corticosteroid, a fixed effects model was used to compare treatments with baseline severity (PGA: mild/moderate) as a covariate. Change from baseline in measurement variables was analysed separately using a mixed model for repeated measures with subject nested within treatment (random effect), and treatment, week, treatment-by-week, age and baseline (fixed effects). The type I error rate was 5% (i.e. significance level) based on a two-sided test. Marginal significance was concluded at 10%. Outliers were excluded based on being greater than 4 standard deviations from the mean.
RESULTS Demographics Sixty-seven patients with AD, and 28 healthy controls were enrolled. The two groups were matched in age and
Skin benefits of moisturising wash for AD children gender. AD subjects were further randomised into three treatment groups and balanced in baseline SCORAD, age and gender.
3
lesion relapse; these were randomly distributed to all treatment groups.
SCORAD Baseline microbiome of AD lesion, AD non-lesion and healthy control sites Relative abundance of Staphylococcus, both at the genus level and at the species level (represented by S. aureus and S. epidermidis), was the highest at lesion sites, followed by non-lesion sites, and the lowest at healthy control sites (Fig. 1, all P < 0.05). Other common skin commensals including Corynebacterium, Micrococcus, Cutibacterium (formerly Propionibacterium) and Streptococcus showed higher relative abundance at healthy control sites and non-lesion sites than lesion sites (Fig. 1, all P < 0.05). Alpha diversity was the lowest at lesion sites, followed by non-lesion sites, and the highest at healthy control sites (Fig. 2, all P < 0.05).
Treatment comparisons between body washes and synthetic bar Tolerance All subjects tolerated the investigational products very well, with no reports of adverse skin reactions related to the use of the products. Five of the 67 subjects reported
Figure 1
SCORAD was decreased for all treatments after 4 weeks of treatment and slightly elevated after 2 weeks of follow up. The magnitude of reduction achieved clinically important difference (8.7 units) compared to baseline for all treatment groups (all P < 0.05); however, it was not significantly different across treatment groups (Fig. 3).
Corticosteroid consumption Four-week corticosteroid consumption was significantly lower for the two body wash groups (6.7 1.1 g in the lipids group and 5.6 1.1 g in the lipids with zinc pyrithione group, respectively) than the bar group (10.1 1.2 g, both P < 0.05). There was no significant difference between the two body wash groups.
Microbiome For the lipid with zinc pyrithione group, the composition of microbiome community was shifted and achieved greater similarity to the healthy control sites; furthermore, the relative abundance of Staphylococcus at genus level
Relative abundance at genus and species level for healthy, lesion and non-lesion sites. © 2019 The Australasian College of Dermatologists
Z Xu et al.
4
Figure 2
Figure 3
Relative abundance and alpha diversity for healthy, lesion and non-lesion sites.
Treatment effect in SCORAD.
and S. aureus at species level was significantly reduced based on 16S rDNA sequencing data (P < 0.05), which was further confirmed by qPCR test (data not shown), while the relative abundance of Corynebacterium, Micrococcus, Cutibacterium and Streptococcus was significantly increased (all P < 0.05), comparing to the mild synthetic bar soap group. Alpha diversity was significantly increased at the lesion sites for the two body wash groups vs. baseline (Fig. 4, both P < 0.05), while the alpha diversity was statistically flat for the mild synthetic bar soap treatment group vs. baseline (Fig. 4, P = 0.23).
DISCUSSIONS Up to 90% of adults with AD have been found to be colonised with large numbers of S. aureus on their skin, which can be cultured not only from eczematous plaques but also from clinically normal skin. In contrast, only 5% of the normal population carry S. aureus which is largely found in the nares and intertriginous areas.4 In AD patients, both lesion and non-lesion skin carry super antigenic-producing © 2019 The Australasian College of Dermatologists
S. aureus, which are capable of modifying T-cell responses, resulting in increased inflammation. It has been shown that a reduction in S. aureus levels on the skin is accompanied by an improvement in AD.5 In addition, microbial diversity at AD lesion sites is significantly lower than non-lesion sites and skin sites from healthy subjects among Caucasians.6–8 Our study revealed similar findings among Chinese children. The comparisons between AD non-lesion sites and healthy control sites suggest that AD skin, even before progression to a symptomatic stage, has increased S. aureus abundance and decreased microbial diversity. Dermatologic therapy for mild-to-moderate AD typically focuses on treatment with topical corticosteroids or calcineurin inhibitors to alleviate AD symptoms, reduce inflammation and prevent flares. An important factor in reducing inflammation is selection of skin cleanser system. Body washes containing topical antiseptics are used as alternative treatments to antibiotics for patients with AD. Those antiseptics include sodium hypochlorite, triclosan, benzalkonium chloride and potassium permanganate.9,10 In this study, we compared two body wash formulas vs. a synthetic bar among mild-to-moderate AD children using 0.1% hydrocortisone butyrate cream as the standard therapy. As the treatment effect was dominated by the corticosteroid, we did not observe an incremental benefit provided by the body wash formulas based on the assessment of SCORAD. However, there was a significant reduction in corticosteroid consumption in the body wash groups. We hypothesise that the corticosteroid reduction benefit was enabled by the moisturising wash technology, which deposits lipids onto skin during the shower and functions synergistically with topical corticosteroid. We observed that the elevated Staphylococcus at the AD lesion sites was reduced and the suppressed normal components of skin microflora were improved, leading to an improved microbial diversity and more balanced microbiota composition in the two moisturising body wash groups (Fig. 4). This is consistent with the report that
Skin benefits of moisturising wash for AD children
Figure 4
5
Treatment effect in relative abundance and alpha diversity.
emollient use increased the microbial diversity in infants at risk for developing atopic dermatitis.11 It appears that zinc pyrithione has an incremental benefit for reducing Staphylococcus and increasing microbial index beyond the lipid only treatment effect (Fig. 4). Zinc pyrithione is an active material that has used for over 50 years to effectively treat dandruff and seborrhoeic dermatitis.12–14 Zinc pyrithione is proven to be effective, even at low concentrations, against both gram-positive and gram-negative bacteria and fungi.12 In vitro testing indicates that the inhibitory concentration of zinc pyrithione is achieved at a level of 10 lg/mL (10 ppm) for S. aureus.12 Zinc pyrithione particles can be deposited and retained on the skin surfaces during the cleansing process. The deposited zinc pyrithione particles can interact with the surface fungal and bacteria cells to control their population and provide persistent benefit.13 Results from the present study indicate that the over colonisation of Staphylococcus on AD skin is averted by treating the skin with a mild yet efficacious antimicrobial body wash. More importantly, it allows the healthy components of natural microbial community to grow back and prevents the Staphylococcus triggered AD pathogenesis. In summary, the present results demonstrated the safety and efficacy of using the investigational body wash formulas in reducing the needs for corticosteroid and improving the healthy composition of skin microbiome vs. the mild synthetic bar soap.
REFERENCES 1. Eichenfield LF, Ahluwalia J, Waldman A et al. Current guidelines for the evaluation and management of atopic dermatitis: a comparison of the Joint Task Force Practice Parameter and American Academy of Dermatology guidelines. J. Allergy Clin. Immunol. 2017; 139: S49–57. 2. Wei K, Stella C, Wehmeyer K et al. Advanced ultra-mild body wash containing dual lipids of petrolatum and glyceryl monooleate improves stratum corneum barrier function and skin surface biomarkers. J. Am. Acad. Dermatol. 2017; 76: AB35. 3. Wei KS, Stella C, Wehmeyer KR et al. Effects of season on stratum corneum barrier function and skin biomarkers. J. Cosmet. Sci. 2016; 67: 185–203. 4. Cho SH, Strickland I, Tomkinson A et al. Preferential binding of Staphylococcus aureus to skin sites of Th-2 mediated inflammation in a murine model. J. Invest. Dermatol. 2001; 116: 658–63. €ussler S, Kapp A et al. Staphylococcus aureus: 5. Breuer K, Ha colonising features and influence of an antibacterial treatment in adults with atopic dermatitis. Br. J. Dermatol. 2002; 147: 55– 61. 6. Kong HH, Segre JA. Skin microbiome: looking back to move forward. J. Invest. Dermatol. 2012; 132 (3 Pt 2): 933–9. 7. Kong HH, Oh J, Deming C et al. Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Res. 2012; 22: 850–9. 8. Byrd AL, Deming C, Cassidy SKB et al. Staphylococcus aureus and Staphylococcus epidermidis strain diversity underlying pediatric atopic dermatitis. Sci. Transl. Med. 2017; 9: eaal4651.
© 2019 The Australasian College of Dermatologists
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9. Barnes TM, Greive KA. Use of bleach baths for the treatment of infected atopic eczema. Australas. J. Dermatol. 2013; 54: 251–8. 10. Majewski S, Bhattacharya T, Asztalos M et al. Sodium hypochlorite body wash in the management of Staphylococcus aureus– colonized moderate-to-severe atopic dermatitis in infants, children, and adolescents. Pediatr. Dermatol. 2019; 36: 442–7. 11. Glatz M, Jo J-H, Kennedy EA et al. Emollient use alters skin barrier and microbes in infants at risk for developing atopic dermatitis. PLoS One 2018; 13: e0192443.
© 2019 The Australasian College of Dermatologists
12. Guthery E, Seal LA, Anderson EL. Zinc pyrithione in alcoholbased products for skin antisepsis: Persistence of antimicrobial effects. Am. J. Infect. Control 2005; 33: 15–22. 13. Schwartz JR. Zinc Pyrithione: a topical antimicrobial with complex pharmaceutics. J. Drugs Dermatol. 2016; 15: 140–4. 14. Food and Drug Administration. 21 CFR Parts 348 and 358. Dandruff, seborrheic dermatitis, and psoriasis drug products for over-the-counter human use: tentative final monograph. Federal Regulation (July 30, 1986)
doi: 10.1111/ajd.13153
ORIGINAL RESEARCH
Skin benefits of moisturising body wash formulas for children with atopic dermatitis: A randomised controlled clinical study in China Zigang Xu1 | Xiaoyan Liu2 | Yueqing Niu3 | Chunping Shen1 | Kate Heminger4 | Laurie 4 Moulton | Amy Yu3 | Tina Allen4 | Lesheng Zhang3 | Feng Yue3 | Jiquan Liu5 | Ying Xu5 | Helen Zhao5 | Lijuan Li4 | Tom Cambron4 | Jian Xu6 | Ed Smith4 | Karl Wei4 1
Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, 2Department of Dermatology, Capital Institute of Pediatrics, 3Procter & Gamble Beijing Innovation Center, Beijing, China, 4 Procter & Gamble Mason Business Center, Mason, Ohio, USA, 5Procter & Gamble Singapore Innovation Center, Singapore City, Singapore, and 6Qingdao Institute of BioEnergy and BioProcess Technology, Chinese Academy of Sciences, Qingdao, China
ABSTRACT Background: It acknowledged that skin care is an important part of atopic dermatitis therapy. However, clinical evidences are limited for the best bathing practices, especially the skin health performance of cleansing products on children’s atopic dermatitis skin.
Correspondence: Karl Wei, Procter & Gamble Mason Business Center, Mason, OH 45040, USA. Email: [email protected] Zigang Xu, MD. Xiaoyan Liu, MD. Yueqing Niu, MD. Chunping Shen, MD. Kate Heminger, PhD. Laurie Moulton, MS. Amy Yu, BS. Tina Allen, BS. Lesheng Zhang, PhD. Feng Yue, MS. Jiquan Liu, PhD. Ying Xu, PhD. Helen Zhao, PhD. Lijuan Li, PhD. Tom Cambron, PhD. Jian Xu, PhD. Ed Smith, BS. Karl Wei, PhD. Consent for Publication from All Authors: Yes. Funding information: This study was supported by a research grant from The Procter &Gamble Company. Conflict of interest: Yueqing Niu, Kate Heminger, Laurie Moulton, Amy Yu, Tina Allen, Lesheng Zhang, Feng Yue, Jiquan Liu, Helen Zhao, Lijuan Li, Tom Cambron, Ed Smith and Karl Wei contributed to and/or conducted this study while employed by The Procter & Gamble Company. The other authors declare that they have no conflict of interest. Study ethics: This study protocol complied with the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the institutional review committee of Beijing Children’s Hospital and conducted per ICH guidelines for Good Clinical Practice. Written informed consent was obtained from the parent/ legal guardian of each subject and verbal assent from each subject. No recognisable photographs were collected from this study. Submitted 28 January 2019; accepted 5 August 2019. © 2019 The Australasian College of Dermatologists
Methods: A randomised controlled clinical study was conducted in China among 4- to 18-year-old children with mild-to-moderate atopic dermatitis to evaluate the skin health effect of three cleansing systems (a mild synthetic bar, an ultra-mild body wash with lipids, and an ultra-mild body wash with lipids and zinc pyrithione) by measuring SCORing of Atopic Dermatitis (SCORAD), consumption of topical corticosteroid and the characteristics of microbiome. Results: Increased Staphylococcus aureus abundance and decreased microbial diversity were observed in atopic dermatitis lesion sites compared with healthy control sites. After 4 weeks of treatment, all three treatments showed clinically important improvement from baseline in SCORAD. Fourweek corticosteroid consumption was significantly lower for the two body wash groups than the bar group. A significant decrease in S. aureus abundance and increase in microbial diversity were observed in the lesion sites for the two body wash formulas, while the microbial diversity was statistically insignificant for the mild cleansing bar group. However, there were no incremental benefits provided by the body wash formulas based on the assessment of SCORAD. Conclusions: These results demonstrated the safety and efficacy of using the investigational body wash formulas with lipids in reducing the needs for corticosteroid and improving the healthy composition of skin microbiome vs. the mild synthetic bar soap. Key words: atopic dermatitis, body wash, microbiomes, skin health.
Z Xu et al.
2
INTRODUCTION Maintaining and enhancing epidermal barrier function plays a critical role in atopic dermatitis (AD) treatment. Use of moisturisers is considered as an effective way to prevent transepidermal water loss (TEWL), prevent flareups and reduce the need for pharmacologic treatment. Bathing for AD patients can be double-edged: it removes crusts, irritants, allergens and bacterial plaques, but at the same time poses further challenges to epidermal barrier integrity.1 The development of moisturising body wash products is one of the more significant changes to affect the personal cleansing market in recent years.2 A key factor contributing to the popularity of these products is that the advanced body wash technologies can be designed to deliver better skin care benefits than regular cleansing body washes or mild bat soaps. The aim of study was to evaluate the health effect of three cleansing systems, a mild synthetic bar, an UltraMild Body Wash with Lipids, and an ultra-mild body wash with lipids and zinc pyrithione (ZPT) among children with mild-to-moderate AD conditions.
MATERIALS AND METHODS Study design This was a randomised, single-blind, parallel group, in home use study consisting of 1-week pre-conditioning phase, 4-week treatment phase and 2-week follow-up phase, conducted over the period May to July 2015. This study protocol was approved by the institutional review committee of Beijing Children’s Hospital and conducted according to ICH guidelines for Good Clinical Practice. Written informed consent was obtained from the parent/legal guardian of each subject and verbal assent from each subject prior to screening. There is no conflict of interest with the products used.
Subject Subjects were recruited from the Outpatient Department of Pediatric Dermatology, Beijing Children’s Hospital and Capital Institute of Pediatrics. The AD group were 4–18 years of age (inclusive), diagnosed as mild-to-moderate AD according to the Physician’s Global Assessment (PGA = 2 or 3) with active lesions involving 5% to 30% of the body surface. Healthy controls were age- and gender-matched to the AD group, with no history or current presentation of AD.
Intervention After baseline visit, the healthy control subjects were discharged from the study, and the AD subjects were randomised into three treatment groups (a mild synthetic bar, an ultra-mild body wash with lipids, and an ultra-mild body wash with lipids and ZPT) and required to wash once daily with the assigned investigational product. The key © 2019 The Australasian College of Dermatologists
ingredients of the mild synthetic bar are sodium lauryl isethionate, paraffin, sodium cocoglyceryl ether sulphonate, glycerine, water etc. The key ingredients of the ultramild body wash with lipids are water, petrolatum, sodium trideceth sulphate, sodium chloride, cocamidropropyl betaine, trideceth-3, fragrance, guar hydroxypropyltrimonium chloride, sodium benzoate, xanthan gum, glyceryl oleate etc. The key ingredients of the ultra-mild body wash with lipids and ZPT are water, petrolatum, sodium trideceth sulphate, sodium chloride, cocamidropropyl betaine, trideceth-3, fragrance, guar hydroxypropyltrimonium chloride, sodium benzoate, xanthan gum, glyceryl oleate, zinc pyrithione etc. Additionally, all subjects were asked to apply 0.1% hydrocortisone butyrate cream to their AD lesion sites once per day until the lesion was gone using the ‘the fingertip unit method’, in place of their previous topical medication. Upon completion of the 4-week treatment phase, subjects discontinued the use of topical corticosteroid for the following 2-week follow-up phase. No other products or medications were allowed except those provided by this study.
Measurement and sample collection During each visit, subjects acclimated in a controlled temperature and controlled humidity room for at least 30 min prior to sample collection. A trained dermatologist, blinded to the three treatment groups, used the SCORing of Atopic Dermatitis (SCORAD) to evaluate the severity of AD. The amount of investigational products and topical corticosteroid used was also collected. Swab samples were collected by applying each swab onto a 10 cm2 skin site in both horizontal and vertical directions for total 50 times. The sampling procedures were performed by trained technicians, and were stored in 80°C freezer until analysed for biomarker and microbiome.3
Statistical analysis A mixed model was used with subject (random effect) and skin type (fixed effect) for comparison of lesion, non-lesion and the skin of healthy controls at baseline. For comparison of 4-week usage of corticosteroid, a fixed effects model was used to compare treatments with baseline severity (PGA: mild/moderate) as a covariate. Change from baseline in measurement variables was analysed separately using a mixed model for repeated measures with subject nested within treatment (random effect), and treatment, week, treatment-by-week, age and baseline (fixed effects). The type I error rate was 5% (i.e. significance level) based on a two-sided test. Marginal significance was concluded at 10%. Outliers were excluded based on being greater than 4 standard deviations from the mean.
RESULTS Demographics Sixty-seven patients with AD, and 28 healthy controls were enrolled. The two groups were matched in age and
Skin benefits of moisturising wash for AD children gender. AD subjects were further randomised into three treatment groups and balanced in baseline SCORAD, age and gender.
3
lesion relapse; these were randomly distributed to all treatment groups.
SCORAD Baseline microbiome of AD lesion, AD non-lesion and healthy control sites Relative abundance of Staphylococcus, both at the genus level and at the species level (represented by S. aureus and S. epidermidis), was the highest at lesion sites, followed by non-lesion sites, and the lowest at healthy control sites (Fig. 1, all P < 0.05). Other common skin commensals including Corynebacterium, Micrococcus, Cutibacterium (formerly Propionibacterium) and Streptococcus showed higher relative abundance at healthy control sites and non-lesion sites than lesion sites (Fig. 1, all P < 0.05). Alpha diversity was the lowest at lesion sites, followed by non-lesion sites, and the highest at healthy control sites (Fig. 2, all P < 0.05).
Treatment comparisons between body washes and synthetic bar Tolerance All subjects tolerated the investigational products very well, with no reports of adverse skin reactions related to the use of the products. Five of the 67 subjects reported
Figure 1
SCORAD was decreased for all treatments after 4 weeks of treatment and slightly elevated after 2 weeks of follow up. The magnitude of reduction achieved clinically important difference (8.7 units) compared to baseline for all treatment groups (all P < 0.05); however, it was not significantly different across treatment groups (Fig. 3).
Corticosteroid consumption Four-week corticosteroid consumption was significantly lower for the two body wash groups (6.7 1.1 g in the lipids group and 5.6 1.1 g in the lipids with zinc pyrithione group, respectively) than the bar group (10.1 1.2 g, both P < 0.05). There was no significant difference between the two body wash groups.
Microbiome For the lipid with zinc pyrithione group, the composition of microbiome community was shifted and achieved greater similarity to the healthy control sites; furthermore, the relative abundance of Staphylococcus at genus level
Relative abundance at genus and species level for healthy, lesion and non-lesion sites. © 2019 The Australasian College of Dermatologists
Z Xu et al.
4
Figure 2
Figure 3
Relative abundance and alpha diversity for healthy, lesion and non-lesion sites.
Treatment effect in SCORAD.
and S. aureus at species level was significantly reduced based on 16S rDNA sequencing data (P < 0.05), which was further confirmed by qPCR test (data not shown), while the relative abundance of Corynebacterium, Micrococcus, Cutibacterium and Streptococcus was significantly increased (all P < 0.05), comparing to the mild synthetic bar soap group. Alpha diversity was significantly increased at the lesion sites for the two body wash groups vs. baseline (Fig. 4, both P < 0.05), while the alpha diversity was statistically flat for the mild synthetic bar soap treatment group vs. baseline (Fig. 4, P = 0.23).
DISCUSSIONS Up to 90% of adults with AD have been found to be colonised with large numbers of S. aureus on their skin, which can be cultured not only from eczematous plaques but also from clinically normal skin. In contrast, only 5% of the normal population carry S. aureus which is largely found in the nares and intertriginous areas.4 In AD patients, both lesion and non-lesion skin carry super antigenic-producing © 2019 The Australasian College of Dermatologists
S. aureus, which are capable of modifying T-cell responses, resulting in increased inflammation. It has been shown that a reduction in S. aureus levels on the skin is accompanied by an improvement in AD.5 In addition, microbial diversity at AD lesion sites is significantly lower than non-lesion sites and skin sites from healthy subjects among Caucasians.6–8 Our study revealed similar findings among Chinese children. The comparisons between AD non-lesion sites and healthy control sites suggest that AD skin, even before progression to a symptomatic stage, has increased S. aureus abundance and decreased microbial diversity. Dermatologic therapy for mild-to-moderate AD typically focuses on treatment with topical corticosteroids or calcineurin inhibitors to alleviate AD symptoms, reduce inflammation and prevent flares. An important factor in reducing inflammation is selection of skin cleanser system. Body washes containing topical antiseptics are used as alternative treatments to antibiotics for patients with AD. Those antiseptics include sodium hypochlorite, triclosan, benzalkonium chloride and potassium permanganate.9,10 In this study, we compared two body wash formulas vs. a synthetic bar among mild-to-moderate AD children using 0.1% hydrocortisone butyrate cream as the standard therapy. As the treatment effect was dominated by the corticosteroid, we did not observe an incremental benefit provided by the body wash formulas based on the assessment of SCORAD. However, there was a significant reduction in corticosteroid consumption in the body wash groups. We hypothesise that the corticosteroid reduction benefit was enabled by the moisturising wash technology, which deposits lipids onto skin during the shower and functions synergistically with topical corticosteroid. We observed that the elevated Staphylococcus at the AD lesion sites was reduced and the suppressed normal components of skin microflora were improved, leading to an improved microbial diversity and more balanced microbiota composition in the two moisturising body wash groups (Fig. 4). This is consistent with the report that
Skin benefits of moisturising wash for AD children
Figure 4
5
Treatment effect in relative abundance and alpha diversity.
emollient use increased the microbial diversity in infants at risk for developing atopic dermatitis.11 It appears that zinc pyrithione has an incremental benefit for reducing Staphylococcus and increasing microbial index beyond the lipid only treatment effect (Fig. 4). Zinc pyrithione is an active material that has used for over 50 years to effectively treat dandruff and seborrhoeic dermatitis.12–14 Zinc pyrithione is proven to be effective, even at low concentrations, against both gram-positive and gram-negative bacteria and fungi.12 In vitro testing indicates that the inhibitory concentration of zinc pyrithione is achieved at a level of 10 lg/mL (10 ppm) for S. aureus.12 Zinc pyrithione particles can be deposited and retained on the skin surfaces during the cleansing process. The deposited zinc pyrithione particles can interact with the surface fungal and bacteria cells to control their population and provide persistent benefit.13 Results from the present study indicate that the over colonisation of Staphylococcus on AD skin is averted by treating the skin with a mild yet efficacious antimicrobial body wash. More importantly, it allows the healthy components of natural microbial community to grow back and prevents the Staphylococcus triggered AD pathogenesis. In summary, the present results demonstrated the safety and efficacy of using the investigational body wash formulas in reducing the needs for corticosteroid and improving the healthy composition of skin microbiome vs. the mild synthetic bar soap.
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