Clinical Study On The Effect Of Acupuncture In Treatment Of Melasma

Background:Melasma is a disturbance in pigmentation in skin.It is a common acquired symmetric brown hyperpigmentation that appears in the face and neck in individuals who are genetically susceptible in this disease.Face is more involved in melasma compare to the neck,and hyperpigmentation most frequently appears in the forehead,malar,upper lip,and chin.According of area of involvement,there are three types of melasma,including centrofacial,malar,and mandibular.Women and men are both susceptible in this disease,but women are more susceptible to this disease,and 90%of the new patients are women.The incidence of melasma increases in pregnancy and is more common during the second or third trimester of pregnancy.This disease is also called chloasma,or mask of pregnancy.Melasma also occurs in women that use oral contraceptives(OCP).The prevalence is variable and it was reported to range between 1.5%and 33.3%.The prevalence of melasma increases during pregnancy and is about 50-70%.Genetic factors and exposure to ultra violet(UV)of sun light are the most important ethilogic factors for melasma.Moreover,pregnancy,oral contraceptive drugs,use of estrogen-progesterone drugs,hyperthyroidism,hypothyroidism,over using of cosmetics,stress,smoking and phototoxic and anti-seizure drugs are other etiological risk factors of melasma.According to theory of Traditional Chinese Medicine(TCM),disharmony between Chong and Ren vessels,Qi and blood disorders and also zang-fu dysfunction,all can lead to melasma.Failure in ascending Qi and blood to the face and neck is a result of disturbance in ascending and descending of Qi.This failure in ascending Qi and blood to the face leads to weak nourishment of face,which causes hyperpigmentation in face and melasma.Generally,there are four main types of melasma based on syndrome differentiation:Liver Qi stagnation,Spleen deficiency,Kidney deficiency,and Stagnation of Qi and blood.Different treatment options are available for management of melsma,including topical agents such as hydroquinone,azelaic acid,retinoids,kojic acid,steroids,chemical peels and recently laser therapy.However,treatment of melasma is still unsatisfactory and remained as a big challenge for dermatologist.Chinese medicine introduces a safe and popular treatment for melasma,which is acupuncture.More randomized controlled trials about treatment of melasma have recently emerges to find more efficient therapies.Most previous studies had methodological defects,some items was insufficient or inadequate in most studies,such as'randomization','allocation concealment and implementation','blinding',“intention-to-treat(ITT)analysis".Many western dermatologists need more evidence to apply acupuncture as a choice for their patients.For these reasons more studies with high quality methodology are needed to investigate the efficacy of acupuncture in treatment of melasma.The aim of this study is to assess the effect of acupuncture in treatment of melasma.Objectives:To evaluate the effect of acupuncture in treating melasma.Methods:Design and setting:A pilot randomized controlled clinical trial was designed and guided by the school of Acupuncture Moxibustion and Tuina in Beijing University of Chinese Medicine,China,and performed at Razi Dermatologic Hospital of Tehran University of Medical Science,Iran,between March 2017 and March 2018.Patients:The number of 53 participants was enrolled in this study.Women with melasma,who had hyperpigmentation on cheeks,forehead and chin,who came to Razi Dermatologic Hospital for treating their disease,were referred to participate in this study.After the initial screening evaluation patients were enrolled in this study if they met all of inclusion criteria,and were excluded if they had any exclusion criteria.Inclusion criteria of this study included women with age between 18-60 years old,who had melasma lesions in face and wanted to participate in this study,signed an informed consent form,and exclusion criteria included women who had used the drug,laser or any other procedures for the treatment of melasma during the past three months,personal or familial history of vitiligo and diseases with pigmentation disorders,pregnancy,breast feeding,using medication like oral contraceptive pills(OCP),history of allergic reaction to hydroquinone,using solarium three months before treatment,and women who didn't want to remain in this study.The trial followed the ethical principles of the declaration and approval obtained from the human research ethics committee of Tehran University Medical Science,Iran.All participants should be signed an informed consent form before their enrollment and could exit from this study at any time.Randomization:The number of 53 participants was finally enrolled in this study.All participants were randomly divided into two groups(26 participants in acupuncture group and 27 participants in Hydroquinone 4%group)by using a "blockrand" package in R software version 3.3.3 by a statistician who hadn't involved in the intervention phase of the study.Interventions:Participants in acupuncture group received facial and body acupuncture as treatment.Acupuncture intervention was performed three times per week for 4 consecutive weeks,totally 12 sessions.Two group points were used including local points and distal points.Distal points include Zusanli(ST36),Sanyinjiao(SP6),Xuehai(SP10)and Quchi(LI11)with even needling technique.Local points include facial points at the rim of melasma lesion.Additional individual points were added,if needed,according to syndrome differentiation of TCM,including Taichong(LR3)with reducing needling technique for liver Qi stagnation,Taixi(KI3),Shenshu(BL23)and Guanyuan(CV4)with reinforcing needling technique for kidney deficiency,Yinlingquan(SP9)and Pishu(BL20)with reinforcing needling technique for spleen deficiency,Geshu(BL17)and Taichong(LR3)with reducing needling technique for stagnation of Qi and blood.After using alcohol for local skin sterilization,disposable filiform needles(0.25 × 40 mm)were inserted perpendicularly at body acupuncture points with proper needling manipulation to induce proper intensity of De Qi(arrival of Qi),after De Qi,the needles were retained for 30 minutes.Disposable filiform needles(0.18 x 25 mm)were inserted transversely at the local points on the face,with the needle tip pointed toward the center of the face lesion.No manipulation was applied on those local points and the needles were also remained for 30 minutes.Hydroquinone 4%local was used for four weeks per night at bed time in control group.All the participants in these two groups were advised to avoid prolonged exposure to sunlight,and also sunscreen cream with sun protection factor(SPF)more than 50 was prescribed for them,to protect against Ultra Violet A rays(UVA)and Ultra Violet B rays(UVB).Outcome measures:The primary outcome measure is Melasma Area and Severity Index(MASI).Patients in both groups were evaluated at baseline and at the end of treatment with MASI score by two uninvolved dermatologists.The secondary outcome measure is treatment score,which was evaluated at the end of the treatment by the same dermatologists according to the photos taken with VisioFace Quick Courage and Khazaka,Cologne,Germany.The value of patient globe satisfaction of treatment was also used as secondary outcome,and was evaluated at the end of the treatment and 1 month after the end of treatment.Statistical analysis:Statistical analysis was conducted by using SPSS statistical software(Version 20.0,IBM)by statistician,who was blinded from allocation of groups.All data was presented as mean ± standard deviation.Chi-Square and independent samples test were used for analyzing the baseline data.Mixed between-within subject ANOVA and independent samples test of difference were used for analyzing data between two groups.Paired samples test was used to analyze the data in each group.P value less than 0.05 was considered statistically significant.Results:Among 53 patients who enrolled in the study and randomized into 2 groups,4 women were stopped treatment during this study:Two women in the hydroquinone group due to side effect of hydroquinone including irritation and itching and 2 women in acupuncture group for individual reasons.Therefore,data of 49 women who completed the trial was included in the analysis.The mean age,body mass index(BMI)and duration since melasma onset were 40.84±7.27 years,23.28±2.80 Kg/m2,and 6.92±5.28 year respectively.Forty-four(89.8%)of participants were married and five(10.2%)were single.Twenty(42.9%)of participants had a history of post-partum melasma and 14(28.6%)had a history of melasma after using OCP.According to area of disease 33(67.3%)had centrofacial melasma,12(24.5%)malar and 4(8.2%)mandibular melasma.Based on Fitzpatrick skin type,one(2%)of patients had Fitzpatrick skin type ?,39(79.6%)type ? and 9(18.4%)type ? and the mean of baseline MASI score was 16.04±8.71.Participants in both intervention groups were similar in terms of age,weight,height,BMI and other anthropometric characteristics(P>0.05).Reduction of MASI scores indicates relieving of melasma in melasma area and severity.Within-group comparison showed that the MASI scores significantly decreased from 16.23±8.68 at baseline to 5.76±3.27 after 4 weeks of treatment in acupuncture group(P<0.001);and from 15.87±8.91 at baseline to 13.08±7.65 after 4 weeks of treatment in hydroquinone 4%group(P<0.001).Compared to hydroquinone 4%group,the difference of MASI score before and after the treatment in acupuncture group was significantly higher(-10.47±9.51 vs-2.78±2.54,P<0.001),indicating acupuncture is more effective than hydroquinone to decrease MASI score after 4 weeks of treatment.According to the digital photos of patient's face,increase of treatment score of melasma indicates positive treatment result with relieving of melasma severity.Compared to hydroquinone group,acupuncture group had significantly higher treatment score at the end of treatment(3.08±1.08 vs 1.90±0.88,P=0.001),indicating acupuncture is more effective than hydroquinone 4%in the treatment of melasma.As a subjective feeling of the patient,higher patient global satisfaction of treatment value also reflects positive treatment result on melasma.There were significant differences between acupuncture group and hydroquinone 4%group about patient global satisfaction of treatment values at the end of treatment(3.67±0.70 vs 2.12±0.97,P<0.001)and 1 month after the end of treatment(3.46±0.83 vs 1.72±0.94,P<0.001),indicating satisfaction of treatment in acupuncture group was higher than hydroquinone 4%group in each time point.However,within-group comparison showed that patient global satisfaction of treatment value significantly decreased one month after the end of treatment compared with that at the end of the treatment in acupuncture group(3.46±0.83 vs 3.67±0.70,P=0.022)and in hydroquinone 4%group(1.72±0.94 vs 2.12±0.97,P=0.001).Between-group comparison also showed that the difference values of patient global satisfaction of treatment between the end of the treatment and one month after the treatment between 2 groups was not significant different(P>0.05),indicating both methods did not show long-term effect for melasma.Conclusion:In this small size pilot RCT,among women with melasma,acupuncture showed better short-term effect of reducing the melasma area size and severity compared with local use of hydroquinone 4%.However,both methods did not show long-term effect for melasma.Further RCTs with larger sample sizes with reasonable power analysis are needed to provide more reliable evidence of the efficacy of acupuncture for melasma.It is needed to get more evidence of the long-term effects of acupuncture by prolonging the treatment course and the mechanism of acupuncture for melasma in future studies.