Résumé
Objective To evaluate the effect of an emollient containing Prinsepia utilis Royle oil extracts and other extracts on clinical symptoms and disease recurrence in children aged 2-12 years with atopic dermatitis (AD) in the remission period.Methods A multicenter,randomized,parallel-group,controlled clinical trial was conducted from December 2017 to September 2018.A total of 297 children aged 2-12 years with moderate AD were enrolled from 5 hospitals in China,and randomly divided into the test group (148 cases) and control group (149 cases).In the acute stage,the two groups were both topically treated with mometasone furoate cream once a day on the skin lesions,and with an emollient containing Prinsepia utilis Royle oil extracts and other extracts twice a day throughout the whole body for 2-4 weeks.The children would be enrolled into the remission stage if their Investigator's Global Assessment (IGA) score was ≤ 1 at following visits.In the remission stage,the test group was only topically treated with the emollient twice a day throughout the whole body,while mometasone furoate cream and the emollient were both withdrawn in the control group.At weeks 4,8 and 12 in the remission stage,the recurrence of AD,eczema area and severity index (EASI),children's dermatology life quality index (CDQOL) and adverse events were evaluated.Statistical analysis was carried out with SAS 9.4 software by using t test for comparison of normally distributed continuous data between two groups,chi-square test for comparison of unordered categorical data,Kaplan-Meier method for analysis of survival rates,Cox regression analysis for evaluating the effect of different therapies on AD recurrence in children in the remission stage,and Logistic regression analysis for analysis of odds ratio (OR) of EASI or CDQOL at week 4 in the remission stage between the test group and control group.Results Of the 297 children with AD,31 breached the clinical trial protocol,and 266 were included in the per protocol set (PPS),including 132 in the test group and 134 in the control group.In the PPS,114 and 106 patients completed the follow-up in the test group and control group respectively,and the recurrence rate was significantly lower in the test group (47,41.23％) than in the control group (84,79.25％;x2 =32.96,P ＜ 0.001).The time to recurrence was significantly longer in the test group(61.99 d ± 2.80 d)than in the control group(39.17 d ± 2.54 d,t =6.03,P ＜ 0.001),and the recurrence risk was significantly lower in the test group than in the control group (Log rank test,x2 =32.02,P ＜ 0.001).After adjustment for age and gender,Cox regression analysis showed that the recurrence risk in the test group was 0.35 times that in the control group (HR =0.35,95％ CI:0.24-0.51,P ＜ 0.01).At week 4 in the remission stage,the EASI score at P50-P75 and P75-P100 in the test group were 0.42,0.25 times that in the control group respectively (95％ CI:0.20-0.86,0.12-0.54 respectively;P =0.02,＜ 0.01respectively).Moreover,the CDQOL score at P75-P100 in the test group was 0.33 times that in the control group (95％ CI:0.17-0.65,P ＜ 0.01).No significant difference in the incidence of adverse events was observed between the two groups (P ＞ 0.05).Conclusion Maintenance treatment with the emollient containing Prinsepia utilis Royle oil extracts and other extracts can markedly reduce the recurrence risk in AD children,improve clinical symptoms,and enhance the quality of life.
Résumé
Objective To evaluate the effects of Prinsepia utilis Royle oil (PURO) on the synthesis of ceramide and expression of acid ceramidase N-acylsphingosine amidohydrolase 1 (ASH1),and to explore the mechanisms underlying its moisturizing and skin barrier-repairing effects.Methods Keratinocytes from human foreskin tissue were classified into 2 groups to be cultured in keratinocyte-serum free medium (K-SFM) with or without the presence of PURO.Enzyme linked immunosorbent assay (ELISA) was performed to measure the level of ceramide in the culture supernatant of keratinocytes at 0,3,8,24 and 48 hours.The back of nude mice was divided into 4 areas,i.e.,test area,matrix area,blank control area and negative control area.Acetone and ether were used to destroy the epidermal barrier in the test,matrix,and blank control areas,then,the former 2 areas were topically treated with emulsions containing 1％ PURO and matrix,respectively,and the blank control area remained untreated.The epidermal barrier remained intact and untreated in the negative control area.Noninvasive methods were used to determine transepidermal water loss (TEWL),epidermal moisture content and skin lipid content in these areas on day 0,1,3,and 7.Skin tissue was obtained from these areas on day 0 and 7 followed by an immunohistochemical study for the quantification of ASH1 expression.Results The level of supernatant ceramide increased with time in the PURO-treated keratinocytes,which was significantly higher at 24 hours and 48 hours than at 0 hour (1.3817 ± 0.100 and 1.3737 ± 0.047 vs.0.7630 ± 0.143,both P ＜ 0.05).The supernatant ceramide was also elevated in the PURO-treated keratinocytes compared with untreated keratinocytes at 24 and 48 hours (both P ＜ 0.05).Noninvasive skin tests showed a gradual decrease in the TEWL,but an increase in the epidermal moisture content and skin lipid content with time in the 3 epidermal barrier-destroyed areas.As far as the test area was concerned,TEWL value was significantly lower on day 3 and 7 than on day 0 (10.85 ± 0.64 and 8.01 ± 0.58 vs.12.65 ± 0.71,both P ＜ 0.05),while a significant increment was observed in the skin lipid content on day 3 and 7 compared with day 0 (29.14 ± 0.40 and 31.30 ± 0.88 vs.27.02 ± 0.65,both P ＜ 0.05),as well as in the epidermal moisture content on day 1,3 and 7 compared with day 0 (13.98 ± 0.28,15.00 ± 0.38 and 15.86 ± 0.18 vs.11.74 ± 0.62,all P＜ 0.05).On day 7,there was a statistical decline in TEWL value,but an elevation in epidermal moisture content,skin lipid content and ASH1 expression in the test area compared with the matrix area and blank control area (all P ＜ 0.05).Also,the expression of ASH1 was upregulated on day 7 compared with day 0 in the 3 barrier-destroyed areas (all P ＜ 0.05).Conclusion PURO may exert skin-moisturizing and barrier-repairing effects by enhancing the synthesis of ceramide and expression of acid ceramidase ASH1.