中国痤疮患者的临床表现 生活方式和情绪与痤疮的相关分析

Zhejiang Universi哆MaSter Thesis 中文摘要 中国痤疮患者的临床表现、 生活方式和情绪与痤疮的相关性分析 浙江大学医学院皮肤科 硕士研究生 黄小芳 导师 朱可建 中文摘要 背景：痤疮是青少年和低龄成年人中最好发的一种皮肤病。它是一种毛囊 皮脂腺的慢性炎症性皮肤病，病变主要累及毛囊皮脂腺单位。痤疮的确切机制尚 未完全确定，目前我们认为发病的病机理关键是毛囊上皮过度角化，皮脂腺分泌 过多，痤疮丙酸杆菌的定植和活动，以及炎症反应。 面部(99％的病例)是痤疮最常见的好发部位，其次是背部(60％的病例) 和胸部(15％的病例)。在临床上，痤疮分为非炎症性皮损(粉刺)、炎症性皮 损(丘疹、脓疱和结节)及疤痕(在某些情况下)。病变通常好发于青春期，以 及青少年后期至20岁之间，该时期患者体内的激素分泌水平改变明显，比如雄性 激素分泌增加。然而，随着年龄的增长，部分个体的痤疮无法痊愈，因此可能给 该个体的身心健康带来严重的后果，比如焦虑、抑郁及自卑。 面部痤疮的病因有很多，疾病的影响因素与生活息息相关。很多方面都与痤 疮有关，包括遗传学、激素、饮食、化妆品、吸烟和压力。 虽然痤疮诊断容易明确，但对痤疮皮损程度的描述及其严重程度的评价都没 有客观的标准。由于痤疮的数量在发病过程可能会有所改变，因此，在患者诊疗 的过程中尽可能每次通过对摄影资料和临床分析来评价痤疮的严重程度。从而制 定相应于严重程度的治疗方案。 痤疮可以发生在各人种和民族。但是，在目前的皮肤科门诊中，痤疮最常见 于非白种人。文章报道，基于社区范围并通过摄影的方法进行研究发现，黑人／非 万方数据 Zhejiang Universi够Master Thesis 中文摘要 洲裔美国人(37％)、西班牙裔／拉丁裔(32％)和亚洲(30％)女性发生痤疮的 比例要高于印度女性(23％)和白人女性(24％)。而且， 通过比较所有皮肤类 型患者的临床表现和治疗，发现肤色较深的患者更易于出现炎症后色素沉着 (PIH)和瘢痕。其中大约三分之二的黑人／非洲裔美国妇女是在治疗痤疮的愈合 阶段出现了PIH。而且持续性和复发性炎症会加重PIH。另外， 还发现非白种人 或白种人都存在的形成瘢痕的后果(好发于下颌和鼻子，甚至形成更严重的痤 疮)。 目前，对于评价同一种族、同一民族人群的痤疮特点的研究仍然非常有限。 而且还有很多与痤疮有关的问题尚未解答，比如，不同皮肤类型患者的临床表现 是否相同，以及基于人口学变量的研究(如性别、年龄)资料也很少。然而，我 们知道，每个患者的遗传背景、生活方式、致病因素、流行病学，以及不同治疗 方法都会带来患者病情的差异性。对痤疮的临床特点、病人的依从性及情绪因素 等进行分析比较，将有助于更好地理解痤疮发病的影响因素，从而改善痤疮的治 疗效果。 目的：研究旨在观察并描述面部痤疮的特点和个体间的差异，评估中国痤 疮患者的临床表现、生活习惯和严重性关联因素之间的相关性。 方法：通过VISIA成像系统拍摄痤疮照片并进行间卷调查，然后进行回顾 性、非干预性、观察性研究来评价痤疮的特点。问卷调查的目的是，了解痤疮的 社会人口学数据及疾病的临床特征、演变趋势、情绪的影响和对以前治疗的满意 度。整个调查未给予任何补偿，病人全部是自愿参与。此外，该调查的参与者不 要求之前的痤疮治疗史，以及是否是第一次咨询痤疮。该研究开始于2015年1 月，对最后一个患者的评估完成于2015年104。本研究对受试对象的年龄要求为 14岁或14岁以上。所有符合条件的受试者都需要了解我们对痤疮进行的皮肤科操 作流程，而且其中不愿意将他们拍摄的照片作为研究数据或无法完成问卷的受试 者将被排除在研究总人数之外。 TTl 万方数据 Zhejiang University Master Thesis 中文摘要 我们在一项研究中粗略汇总患者的痤疮病史，以便于进一步了解痤疮的特 点。该研究涉及的痤疮相关问题，包括：痤疮史和特点，生活方式和饮食习惯， 痤疮治疗过程，皮肤护理及化妆品的使用。本研究中，我们通过Skindex．29情绪 量表来评估影响痤疮的情绪因素。每个病人的摄影资料都采用VISIA成像系统， 该成像系统从三个角度捕获人脸(右，前，左)，以便于被用来评估痤疮。在该 研究中，我们对各个区域的痤疮严重程度，位置和病变类型进行评估。然后采用 痤疮综合分级系统进行总体评估。具体而言，我们通过乘法计算总分数，病变部 位(额头=2，右脸颊=2，左脸颊=2，鼻子=1，下颌=1，胸部和上背部=3)， 严重程度(无病变=0，黑头粉刺=1，丘疹=2，脓疱=3，结节=4)。成绩1．18 为轻度；19．30为中度；31—38为重度；>39为非常严重。同时，我们将痤疮分为 三组：粉刺(非炎症性)、丘疹和脓疱(炎症性)和结节或囊肿。将痤疮的病变 位置划分为五个面部区域(右脸颊、左脸颊、前额、T区、下颌区)和一个身体 区域(背部)。其他的临床表现，如红斑、皮脂分泌亢进、瘢痕和炎症后色素沉 着也进行主观的评价。但该研究中并没有评估性别与痤疮的严重程度之间的关 系。 该研究中的Skindex一29的情绪影响因素的评分方法与美国原始版本的评分方 法是相同的。对于每一个项目，受试者选择一项符合自己本人痤疮发生频率的选 项(从来没有，很少，有时，通常，所有的时间)，并予以相对应的分数1．5。然 后对所有与情绪因素指数有关的数据进行统计，其总分波动于10(无负性情绪影 响痤疮)至50(最大的负面情绪影响痤疮)。 整个研究中，我们使用微软Excel(微软Office 2010，Redmond，WA， USA)和社会科学统计软件包(22版IBM，美国)进行各种统计分析。我们用汇 总表及描述性统计来统计相关数据的参数。分析连续变量，中位数，均数，标准 差，标准误，最大值及最小值。同时，还分析了分类变量，百分比分布和频率。 然后用交叉表、卡方检验和回归分析的方法来确定生活方式与痤疮严重程度之间 的相关性。通过单因素方差分析和最小显著性差异(LSD)检验来确定情绪因素 与痤疮严重程度之间的相关性。其中P<0．05，则表示结果具有统计学意义。 IV 万方数据 Zhejiang University Master Thesis 中文摘要 结果：共有100名中国患者参加了这项研究(63名女性和37名男性)。平均 就诊年龄女性为1 8Y，男性为20岁(年龄段为14．46岁)。其中大多数患者的皮肤 类型为IV(81％)，只有19％的患者的皮肤类型为III。受试者中的48％是在外来 务工人员(37．5％为男性，62．5％为女性)，而52％的受试者(36．5％为男性； 63．5％为女性)为家庭主妇或学生。受试者主要是单身(83％)，只有17％的人为 已婚。 有部分受试者(男性：59．5％，女性：44．4％)，12．19岁之间开始出现痤 疮；2．7％的男性和4．8％的女性在青春期前发病；剩下的37．8％的男性和50．8％的女 性的发病年龄为20岁或20岁以上。受试者年龄发病的平均值和中位数分别为19．25 和18．5。 大多数的受试者(包括31名男性和49名女性)表示，他们的痤疮在发病以来 几乎是一直存在的状态(持续性痤疮)，而其余受试者则陈述他们经历过无粉刺 期(复发性痤疮)。共有48例持续性痤疮患者从青春期就开始出现痤疮(43．75％ 为男性，56．25％为女性)，而17例复发性痤疮患者(76。5％为男性，23。5％为女 性)则是在20岁或20岁以上才出现痤疮。 大多数的受试者(97％)的痤疮累及到多个面部区域(脸颊，下颌，额头， 颞部)，而成年人与青少年的痤疮严重程度是相似的。混合性面部痤疮(炎症性 和非炎症性病变同时存在)是最常见的痤疮形式。受试者在额头、下颌、面颊发 生粉刺性病变的比例几乎是相等的。男性和女性的炎症病灶都是在右脸颊和下颌 区最为明显，其次在左脸颊和前额，最少发生在T区。3％的受试者的左颊部和下 颌区最主要的问题是结节，但病变均未涉及T区。37％名受试者表示痤疮涉及到 躯干部。其中，大多数受试者有中度痤疮(48．6％)，其次是极重度痤疮 (19％)，然后是轻度和重度痤疮(各占16．2％)。痤疮严重程度从33％轻度、 ＼ 47％中度、12％重度和8％极重度。我们发现极严重的痤疮主要发生在男性，即便 本研究中女性的病例数是男性的两倍。 61％的受试者接受过前期的治疗，但只有三分之一的患者对治疗结果满意， V 万方数据 Zhejiang University Master Thesis 中文摘要 而接受过前期治疗的受试者中的大多数表示，他们已经至少使用过一种类型的外 用药治疗(非处方药或处方药)。我们发现，接受过前期治疗患者的痤疮严重程 度高于未接受前期治疗者，但这个结果并不显著(P>O．05)。 据报道，有12N男性和20名女性有痤疮家族史(共32名患者)。其中，23例患者 的痤疮在12—19岁出现(青春期)，9例患者的痤疮在20岁以后出现。阳性家族史 的痤疮患者的平均发病年龄低于阴性家族史的痤疮患者(17．7岁VS．19．3岁)。研 究表明痤疮的严重程度从轻微N21．9％，中度28．1％，重度25％及未 记录 混凝土 养护记录下载土方回填监理旁站记录免费下载集备记录下载集备记录下载集备记录下载 的25％。 在我们的研究中，阳性家族史的痤疮患者发生重度痤疮的频率(P<0．05)高于轻 度和中度痤疮。 对于面部痤疮，有三分之二的受试者存在红斑(76例)，其中男性占 42．1％，女性占57．9％。红斑的好发部位依次为下颌，T区和前额及脸颊。在本研 究中，与青少年和年轻人相比，我们发现成年男性和女性红斑发生率有上升的趋 势。而在20岁以后红斑的发生率呈下降的趋势，红斑最好发于20．25岁的受试者 中。 根据我们的观察，76位受试者出现皮脂分泌亢进(表2)。在这些受试者 中，男性和女性都有中度痤疮(54．8％为男性，55．6％为女性)，其次是35．5％的 男性的严重痤疮，以及26．7％的女性的轻度痤疮。据报道，有皮脂腺分泌亢进的 女性的17．7％都患有非常严重的痤疮，而只有极小部分的男性是轻度痤疮。另 外，我们还发现，只有大约一半的患有皮脂腺分泌亢进的受试者在后背部出现痤 疮病变。 77％的受试者出现痤疮疤痕(主要指萎缩性的)。研究表明，与其他人相 比，患有混合痤疮皮损的男性和女性更容易出现痤疮疤痕。值得注意的是，易于 出现痤疮疤痕的个体中，有极个别的患者仅仅患有炎症性(2例)或非炎性(2 例)病变。与PIH，红斑类似，受试者的疤痕多发生于20．25岁(53．2％)，其次 是26岁或26岁以上(32．5％)，最后是青少年(14-3％)。无论是男性还是女性， 瘢痕主要出现在脸颊(左脸颊和右脸颊都出现瘢痕的占76．6％)，其次是T区(男 性&28．6％，女性&20．8％)，下颌区(男性占33．8％，女性占23．4％)，和额头 VI 万方数据 Zh日iang Universit)，Master Thesis 中文摘要 (男性占15．6％，女性占6．5％)。我们发现，有疤痕患者中的一个极小的比例 (9．1％)(主要是男性患者)呈现出萎缩性和增生性瘢痕共存的状态(大多发生 于下颌区)。 该研究中有大部分患者有PIH。对于男性和女性，PIH最好发的面部区域为下 颌区，其次是脸颊、额头、T区。PIH好发于20．25岁的成年受试者(51．1％)，较 少发生于26岁或26岁以上的受试者(34％)，以及最不易发生于青少年 (14．9％)。值得注意的是，本研究中青少年受试者的数量较少。对于患有PIH的 51．1％的受试者，其中有20．8％患有轻度痤疮，52．1％患有中度痤疮，其余为重度 痤疮。研究中有72名受试者同时出现PIH与红斑。 在这项研究中，我们需要大多数女性提供月经周期的情况。但是，本研究并 不分析初潮年龄和月经持续时间。女性参与者中的17．5％为月经周期不规则，这 些患者的年龄在20岁及20岁以上。但是，在月经周期不规则的女性中，只有1名 女性患有多毛症，其余的女性均没有其他内分泌异常疾病。此外，女性普遍认为 月经周期与痤疮恶化是相关的，大多数女性强调痤疮好发于月经周期前，但仍然 有小部分女性的痤疮好发于月经周期后。 根据卡方检验和交叉表检验，我们发现治疗前、家族史、行为和生活方式因 素指标(饮酒、吸烟、便秘、失眠、职业暴露、体力活动、锻炼、护肤品及化妆 品的使用)的P都大于0．05，这说明各指标均不是独立的显著影响因素(表4)。 但是结果确定了一个事实，即上述因素与严重程度之间可能没有相关性。此外， 膳食摄入、日常生活的压力及工作压力均需作为重要因素而单独评估。 我们根据回归分析，将所有因素拟定为自变量，将严重程度的程度作为因变 量，研究发现，只有保湿因素的评估系数存在显着差异，这表明润肤霜与严重程 度之间是相关的，并且呈正相关关系。 该项研究中评估的护肤品包括润肤霜，洗面奶和防晒霜。对于洗面奶，所有 受试者使用的洗面奶均为非处方药，没有受试者使用规定的洗面奶。因此，我们 并没有对洗面奶进行进一步的研究。在这项研究中，只有不到一半的受试者使用 防晒霜，60％的受试者表示他们在日常生活中很少／从不使用防晒霜。研究发现， VII 万方数据 Zhejiang University Master Thesis 中文摘要 痤疮的严重程度与防晒霜的使用水平呈负相关。而在这项研究中，更多的受试者 数据支持这种负相关的关系，而且非每日使用防晒霜的受试者较每日使用防晒霜 的受试者更易出现极重度痤疮(85％与15％，P<0．05)。本研究中，24％的受试 者在日常生活中很少使用润肤霜，而研究显示痤疮的严重程度和保湿的水平之间 呈负相关关系，这表明减少或不使用保湿品会增加痤疮的严重程度(P<0．05，呈 显著相关)。 这项研究中46％的女性使用化妆品来遮盖痤疮和／或PIH及痤疮疤痕。研究表 明，化妆品的使用率和痤疮严重程度之间呈正相关关系，而化妆品可能是顽固痤 疮(主要是黑头粉刺)和局限在额头和脸颊区痤疮的原因。但是，我们的研究表 明使用化妆品和不使用化妆品受试者的痤疮没有明显区别(P>O．05)。 在本研究中，吸烟和酒精摄入量与痤疮严重程度无相关性，由于本研究中这 些因素的摄入率并不清楚，造成我们分析的局限性。在这项研究中，有42％的受 试者(57．1％为女性，42．9％为男性)患有便秘。53％的受试者(64．2％为女性， 35．8％为男性)陈述他们很少／从未有便秘，5％的受试者(都为女性)陈述他们经 常便秘。即使痤疮的严重程度与便秘之间呈正相关，痤疮的严重程度对于经常、 偶尔及很少／从未便秘的受试者来说仍然是相同的(P>0．05)。 这项研究的37％的受试者(其中包括59．5％的男性和40．5％的女性)表示其有 睡眠或失眠问题。中度痤疮(40．5％)最易发生失眠，其次是轻度痤疮 (37．8％)，最后是重度到极重度痤疮。可见，痤疮严重程度与失眠程度呈正相 关。但是，这并没有统计学意义(P>0．05)。 仅有极少数的受试者提及职业暴露的问题(6％)。其中67％的受试者为中度 痤疮，33．3％为轻度痤疮。由此可见，痤疮的严重程度和职业暴露之间的关系呈 正相关，虽然这并没有统计学意义(P>0．05)。 大多数受试者表示，他们在曰常生活中有一些锻炼或体力活动。只有少数的 受试者(25％)表示他们很少运动。而研究表明，痤疮的严重程度和运动之间呈 负相关，这说明运动量降低的受试者将出现更严重的痤疮。虽然这并没有统计学 意义(P>0．05)。 VIII 万方数据 zhejiaIlg UniversiW Muter Thesis 中文摘要 在这项研究中，共有80％的受试者表示，他们有时或经常晒太阳。与那些很 少晒太阳的受试者相比，经常晒太阳的受试者更易于发生重度至极重度痤疮 (80％VS．20％)。虽然线性方程系数表说明了痤疮严重程度与阳光照射水平呈正 相关的事实也支持上述发现。但是研究结果并没有统计学意义(P>0．05)，这意 味着太阳暴露与痤疮严重程度之间没有相关性。 以0．10为压力范围，在这项研究中，平均每天的压力为3．64，这意味着受试 者的总体压力等级是温和的。我们还计算各个痤疮严重程度下的平均日常压力等 级。如表5所示，日常的压力越高，痤疮的严重程度就越高。相反地，日常压力 可能只是极重度痤疮的一个影响因素。但是，结果并没有统计学意义(P> 0．05)，这表明日常压力与痤疮的严重程度之间没有相关性。 我们询问受试者，他们觉得他们的工作带来的是心理上还是身体上的压力。 31．25％的受试者表示，他们的工作带来的是身体上的压力，而68．75％的受试者则 表示在他们的工作带来的是心理上的压力。我们发现，工作带来心理压力的受试 者的痤疮要比身体压力的受试者的痤疮更为严重(75％VS．25％)。 与无奶制品摄入的受试者相比，有奶制品摄入的受试者更易于发生中度至极 重度痤疮(59．7％VS．403％)。然而，回归分析表明，痤疮的严重程度与奶制品 摄入量没有相关性(P>O．05)。这项研究中，一半的受试者摄入甜食。结果表 明，甜食摄入量与痤疮严重程度呈正相关，即甜食摄入的增加会加重痤疮的严重 程度，但是摄入或者不摄入高糖食物与痤疮的发生并没有相关性(P>0。05)。 39％的受试者以摄入油性食品为主，其中，多数呈现中度痤疮。但是痤疮的严重 程度的与摄入高油脂食物之间并没有统计学差异(P>0．05)。在这项研究中，大 约三分之一的受试者摄入辛辣食物。其中有一项估计表明，如果一个人食用辛辣 食物，那么其痤疮的严重程度也会增加。但是，结果并没有统计学差异(P> 0．05)，即痤疮的严重程度与食物是否辛辣无关。 46％的受试者报告了其他疾病。目前最常见的疾病是过敏(49．1％)，其次是 抑郁症(19．3％)，焦虑(17．5％)和肥胖(14．1％)。研究中的所以受试者均否 认使用的药物可能会加重痤疮，而受试者提供的最常用药物为抗组胺药和维生 IX 万方数据 Zhejiang University Master Thesis 中文摘要 素。 Skindex．29的平均情绪评分为31．58，这可能意味着，该研究中，受试者的痤 疮极有可能受到情绪影响。根据回归分析表和皮尔森相关分析，痤疮严重程度的 评估系数为0．259，相关系数为0．029，这表明痤疮严重程度与kindex．29的情绪评 分呈正相关。但是，结果并没有显著的统计学意义(P>0．05)。根据单因素方差 分析，评估Skindex．29情绪量表的平均值与各组痤疮严重程度的0．05的偏离水平。 LSD试验表明，事实上Skindex．29情绪量表中得分最高的受试者患有非常严重的 痤疮。 结论：[1]青春期痤疮对男性影响更大，而成年期痤疮对女性影响更大； [2]经前痤疮发作与青春期痤疮和成人痤疮相关；[3]大多数青春期痤疮和成人痤 疮均有类似的面部痤疮分布特点；[4]阳性家族史患者的痤疮进一步加重的风险 更高；[5】未进行日常防晒和润肤的患者的痤疮进一步加重的风险更高；[6]进行 或者未进行前期治疗的患者，他们之间痤疮的严重程度没有明显差异；[7]患有 重度痤疮的患者，其病情更易受到情绪因素的影响；[8]其他的混杂因素，如吸 烟、饮酒、便秘、压力、失眠、日晒和化妆品与痤疮的严重程度之间均没有明显 的相关性。这项研究是对100例中国人痤疮面部分布的一个客观评价。研究结果 不仅对迸一步了解痤疮的l临床特点有帮助，还为不同人种的痤疮研究资料提供一 些新的数据。 X 万方数据 Zhejiang University Master Thesis 英文摘要 _______—，——__，'_______-—●—●-___●______————________-，——，——________———●—'______●●———_-_____●●●-————●____-———————______————__●——————————————— UNDERSTANDING oF CLINICAL PRESENTATION， LIFESTYLE FACToRS AND EMoTIoNAL IMPACT COI沁LATED WITH ACNE IN CHINESE PATIENTS． Department of Dermatology and Rheumatology Sir Run Run Shaw Hospital College of Medicine，Zhejiang University Postgraduate Clarissa Dwipuspa Wijaya Supervisor Dr．Kejian Zhu Abstract Background： Acne vulgaris remains to be one of the most common diseases afflicting humanity． It is the skin disease most commonly treated by physicians．Due to different genetic background and lifestyle，the prevalence and risk factors of acne are unlikely consistent． These factors are considered to be relevant to the course of disease；however，limited research has evaluated them among people with ache in the same racial and ethnic group． Objective： To describe various features of facial acne，to evaluate the correlation of clinical presentation，behaviors，and associated factors in the severity of acne among Chinese patients． Method： Non-interventional，retrospective，observational study was carried out to evaluate the clinical characteristics and lifestyle factors associated with acne in patients at a dermatology visit for acne．Acne severity was assessed by picture taken with VISIA and questionnaire including medical history，disease evolution，lifestyle habits，previous treatments，skin care and quality of life．Cross tabulation，chi square and regression Xl 万方数据 Zhejiang University Master Thesis 英文摘要 analysis test were used to find the correlation and PO．05)while other factors were not significantly associated fP>O．05)．Patients with more severe acne tend to have higher emotional scale score of Skindex一29，yet there was no association between acne severity and emotional scale score of Skindex．29． Conclusions： The study represents an objective assessment of the facial distribution of acne lesions in Chinese patients presenting to our dermatology clinic．Majority of the data indicates that the acne distilbution in adults is similar to that in adolescents．Adolescent acne tends to affect men while adult acne tends to affect women．Adolescent acne iS more likely caused by hereditary factors，while adult acne is more likely cause by lifestyle factors．Family history of acne，un·daily use of moisturizer and sunscreen were significantly associated with acne severity． 万方数据 Zhej协g universi谚Master ThesiS一————————————————A—ck—no—w—le—d—ge—m—ent ———_=L——=二————————二_———————————————————————————————————————————一一—— Abbreviation PIH Post inflammatory hyperpigmentation GAGS Global acne grading system OTC Over the counter IPL Intense pulse light SPF Sun protection factor TEWL Trans-epidermal water loss DLQI Dermatology life quality index PSU The pilosebaceous unit LAT L-type amino acid transporter DHT Dihydrotestosterone IGF Insulin-like growth factor —————————————————————————————————————————————一 XIll 万方数据 Table of Content ACKNOWLEDGEMENT ．I 中文摘要 II ABSTRACT ．XI ABBREVIATION ．XIII 目录 正文 1．INTRODUCTION ．．1 2．MATERIALS AND METHODS 5 2．1 STUDY DESIGN．． ．． ． ． ． ． ．．． ． ．． ．． ． ．． ． ．． ． ． ． ．．5 ：2．2 PATIENT SELECTION．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．5 2．3 STUDY ASSESSMENTS．．．．．．．．．．．．．．．．．．．．．．．．．．．．． ．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．。．．．．．．．．． ．．．．．．．．．．．．．．．．．．．．．．．．．5 2．4 ANALYSIS． ．． ．．． ．． ．． ． ． ． ．．． ．． ．． ．． ． ． ． ．．． ． ．． 6 3．RESULTS 7 ：；．1 DEMOGRAPHICS．．．．．．．．．．．．．．．．．．．．．．．．．．．． ．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．7 ：；．2 ACNE HISTORY．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．7 3．3 TYPE OF ACNE． ． ．． ． ． ． ． ． ．． ．． ． ． ．． ． ．7 3．4 CLINICAL PRESENTATION ． ．． ． ．． ． ． ． ．． ．． ．． 。 ． ． ． ．1() 3．6 BEHAVIORS AND LIFESTYLE FACTORS ．．17 ：；．7 COMORBIDITY AND MEDICATIONS．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．．33 ：；．8 EMOTIONAL IMPACT． ． ． ．． ． ． ． ． ． ．． ． ．． ． 33 4．DISCUSSION． ． ．． ．． ．． ． ． ． ． ． ．．． ． ．． ． ． ． ． ．． ．．．：；6 5．CONCLUSIONS ．．44 6．LIMITATl0NS ．45 REFERENCES 46 LITERATURTE REVIEW 54 作者简历 一73 万方数据 垫鱼!竺曼坐堡!!墅堡坚竺!!!里型! 堡塑塑型竺 Understanding of clinical presentation，lifestyle factors and emotional impact correlated with acne in Chinese patients． Department of Dermatology and Rheumatology Sir Run Run Shaw Hospital College of Medicine，Zhejiang University Postgraduate：Clarissa Dwipuspa Wij aya Supervisor：Dr．Kej ian Zhu 1．Introduction Acne vulgaris remains as one most universal skin diseases encountered in both adolescents and young adult．It consistently represents the top three most prevalent skin diseases in the general population，as found in large studies within France，UK and USA． [81-831 Similar numbers are reported for young aduRs in several countries throughout the world．【84】It is a chromc inflammation of the pilosebaceous componems，involving the sebaceous gland，connecting duct and hair follicle。The exact mechanism of acne has not yet been entirely discovered，though it is assumed that follicular epidermal hyperproliferation，excessive sebum production，presence and activity of Propionibacterium acnes，and inflammatory response are the key pathogenesis．。11 The basement membrane of PSU，the same epidermal-dermal barrier seen in the skin，surrounds the PSU and provides structural support for its basic components including the hair，hair follicle，erector pili muscles，and sebaceous gland．The basement membrane is lined with basal stem cells that，given the correct hormones from the body， develop into sebaceous cells and keratinocytes that produce oil and hair， correspondingly．Squamous epithelial cells，also known as ductal lining cells are lining the central canal of the PSU follicular part．When stimulated by androgens hormones， these cells(the sebaceous cells，keratinocytes，and ductal lining cells)are activated and start to proliferate．When the proliferating ductal lining cells unable to escape the PSU infimdibulum，they form a plug，backing up the production of sebum and hair growth that remain undemeath it．The pressure within the unit compromises the accessibility of diffusible oxygen to cells undemeath，constraining their metabolism and providing an 1 万方数据 Zhejiang University Master Thesis Introduction ideal，anoxic environment for flora(Proprionibacterium acnes) to grow．Moreover，the overproduction of sebum delivers nutrients supply in fatty acids form to rapidly multiplying bacteria within the PSU． The plugged PSU surpasses the retention capacity of its structural basement membrane once growth underneath，bursts and exposes its contents to our body’S immune system．P．aches is an anaerobic，Gram-positive rod present in a natural part of Our skin’S flora as well as the main initiator linked to the inflammation of acne． Naturally discovered on the skin surface，Malassezia furfur is yeast that also contributes to the pathogenesis of acne．White blood cells immediately recognize the lipoproteins of this foreign pathogen through receptors，specifically the Toll—like receptor一2 and Toll— like receptor一4，stimulating keratinocytes to secrete interleukin一6 and interleukin一8 and giving rise to erythematous inflammation．[96,97】Ultimately，inflammatory mediators recruit white blood cells to support an attack against the pathogens，yielding in the erythematous pustule formation．Over time，the inflammatory response restores the damage within the PSU and precedes the skin to normal． Face(99％of cases)is the most common area affected by acne，followed by back (60％of cases)and chest(1 5％of cases)．[21 Clinically,it is categorized by non． inflammatory lesions(comedones)，inflammatory lesions(papules and pustules)and nodules，and in some cases，scarfing．[31 According to the Global Burden of Disease (GBD)study，approximately 85％of young adults aged 12—25 years were affected丽tll acne．[801 This condition typically appears during puberty and normally resolves in the late teens to early twenties，the years when hormones such as testosterone are increasing． Then again，for several individuals，this condition could stay and may have trigger several serious physical psychological outcomes including anxiety，depression and lower seIf-esteem．[4,5-81 Facial acne is a multifactorial pathophysiology condition as well as its effect on day—to-day performance．A range of aspects have been linked to acne，including genetics，hormones，diet，cosmetics，tobacco use and stress．【911 o】 Although effortless to identify，the polymorphic description of acne and its diverse range of involvement do not permit humble evaluation of its severity．As the acne lesion may differ in quantity throughout the disease progress，countless measurements have 2 万方数据 been created，based on photographic documentation and clinical analysis，to evaluate the severity of acne vulgaris．Additionally，acne measurements would be essential as 11 long as the treatment regimens of acne yielded an all-or—none response．11 Ache vulgaris could affect people of all races and ethnicities．However，it is now the most familiar diagnosis in dermatological clinics among non-Caucasian patients．。12‘ 171 Acne was discovered to be extremely significant in Black／African American(37％)， Hispanic／Latina(32％)，and Asian(30％)women，more than in Indian(23％)and 【18】 Cancasian women (24％) women in a community．based photographic study． Although the pathophysiology and treatment options among all skin phototypes are comparable，patients with darker skin colors have the tendency to be seen more with postinflammatory hyperpigrnentation(PIH)and keloids．[19,20]Around two thirds of Black／African American women encounter PIH，which commonly appears throughout the healing process following acne treatment．[18,19]Persistent and recurring innammation Can worsen PIH．[21,22]Additional general potential outcome in non— White／Caucasian populations is keloidal SCarS，which appeared regularly along the 7,22,231 {a、vline部[1d仇】n k a11d often linked with more severe acne．[1 There have been very narrow research evaluating acne features among people with the same racial and ethnic group．Countless questions relating to acne endure， embracing whether diverse presentations based on different skin phototypes are present， or based on demographic variables such as gender then age．However，as a result of different genetic background and lifestyle，the risk factors and prevalence of acne are doubtful to be consistent，and the application of different treatments also varies in each acne patients．A broader understanding of clinical features，patient behaviors，emotional impact of acne will assist in enhancing treatment upshots in this progressively distinct Chinese population． Despite its prevalence，misconceptions of the initiating and exacerbating factors that influence the development and severity of acne continue to last．By providing data that accurately portray the epidemiology，genetics，comorbidities，risk factors，and treatment associated with acne vulgaris，we hope to improve the awareness of the demographics affected by this condition and lead to imperative changes in patient education and treatment． 3 万方数据 Zhejiang University Master Thesis Introduction The objective of this study was to portray various clinical features of acne in Chinese patients，to evaluate the correlation of clinical presentation，behaviors，and associated factors in the severity of ache． 4 万方数据 兰堕!竺曼坐!!竺堑堕坚箜塑坠型!些竺型!竺堡坚些唑 2．Materials and Methods 2．1 Study design A retrospective，non—interventional，observational study was carried out to appraise the features of ache in patients via pictures taken by VISIA Canfield Imaging System and questionnaires．The questionnaire inspection screened for participant self-reported signs reliable with ache and captured data on sociodemographic and clinical features， behaviors，emotional impacts，and previous treatment satisfaction．No compensation was offered and patients’participation was voluntary．Moreover，the participating subjects could have or not be previously treated and the study visit was not obliged to be the first consultation for acne．The study started on January 20 1 5 and the last subject was enrolled on October 20 1 5． 2．2 Patient selection The subj ects selected for this study were aged 1 4 years old or older．All eligible subjects visited OUY dermatology practice for ache was offered the chance to participate． Subj ects were excluded if they were unwilling to have their pictures taken for documentation or were unable to complete the questionnaire． 2．3 Study assessments A thorough patient history containing acne related questions were gathered to understand the characteristics and features of acne in participating subj ects．Acne associated questions included acne history and characteristics，lifestyle factors and dietary intake．which in the previous literatures have been linked with acne and the use of acne treatments，skin regimens and make up．Emotional impact of acne was assessed by emotional subscale of Skindex一29． Photographic documentation of each subject was taken with VISIA Canfield Imaging System．This imaging system captured three angle of the face(right，front，left)， which then was used to assess acne．In this study，acne was assessed by its severity，and its location and type of lesions per each area．Global assessment was calculated using The Global Acne Grading System．[791 Specifically，it is the total of the local scores which is calculated by multiplying factor(forehead=2，right cheek=2，left cheek=2， nose=1，chin=1，chest and upper back=3)and grade(no lesions 2 0，comedones 5 1， 气 万方数据 papules=2，pustules=3，and nodules 2 4)．A score of l一1 8 is considered mild；19_30 moderate；3 1．38 severe；and>39 very severe．Second，acne was classified into three groups：comedones(non-inflammatory)，papules and pustules(inflammatory)，and nodules or cysts．Then，location of acne lesion across the five facial areas(right cheek， left cheek，forehead，temples，mandibular area)and on one boay area(back)was recorded．For each facial region，type of lesions present was identified．Additional clinical presentations such as erythema，hyperserborrhoea， scarring， and postinflammatory hyperpigmentation was also assessed subj ectively．Nevertheless， relationship between gender and acne severity was not evaluated in this study． Emotional impact of Skindex一29 in this study implemented the sanle scoring method as the original American version．For each item，the subj ects endorsed the frequency of a given acne—related experiences(never,rarely，sometimes，often，all the time)，and the response were scored on a scale of 5．The total score is a SHill of scores for all items providing an index of emotional impact，it Can range from 1 0(no negative emotional impact of acne)to 50(the greatest negative emotional impact of acne)． 2．4 Analysis All the statistical analysis was carried out using Microsoft Excel(Microsoft Office 20 1 0，Redmond，WA，USA)and Statistical Package for the Social Sciences(version 22．0 IBM，USA)．Summary tables as well as descriptive statistics were calculated for the entire parameters of interest．For continuous VariabIes，the medians，means，standard errors，standard deviations，the maximum and minimum values were analyzed．For categorical variables，percentage distributions and frequency were also analyzed．Cross tab，chi—square and regression analysis was used to define correlation with statistical significance measured at P<0．05． 6 万方数据 3．Resuits 3．1 Demographics In this study，a total of 1 00 patients were enrolled，from China(N=99)and Malaysia(N=1)．Mean the time of visit age was 1 8 in men and 20 in women(ranging from 1 4．46 years)．Detailed demographic characteristics of the subjects are specified in Table 1；remarkably，all of the patiems are Asians．Among them，the majority had skin phototype IV(8 1％)and only 1 9％had skin phototype III．Outside of home employmem was reported by 48％subjects(37．5％men，62．5％women)，whereas 52％of the patients f36．5％men；63．5％women)implied that they were either homemakers or students．The patients in the group were predominantly single(83％)，while 1 7％of them were married． 3．2 Aene history 3．2．1 Onset age Sub4 ects were requested to bring to mind when acne lesion first emerged，then prepubertal(<1 2 years)，adolescent(1 2—1 9 years)，young adult(20-25 years)or after 25 years were recorded as replies．A small majority of the men(59．5％)，women(44．4％) recollected that acne began between 1 2—1 9 years of age；2．7％men and 4．8％women reported prepuberty onset；the remaining 37．8％men and 50，8％women reported onset at age 20 or older(Table 1 1．The mean and median of the self-reported age onset of acne for overall subjects were 1 9．25 and 1 8．5 correspondingly． 3．3 Type ofaene While asked to describe the course of acne，majority of the subjects consisted of 3 1 men and 49 women stated that their acne had been existent for all or most of the time since the onset of the disease(persistent acne)；while the rest stated substantial period of time without acne(relapsing acne)．A total of 48 patients with persistent acne had acne started in adolescence(43．75％men，56．25％women)，while 17 patiems with relapsing acne(23．5％men．76．5％women)had acne started at the age of 20 or older． 7 万方数据 Zhejiang University Master Thesis Table 1 Demographic characteristics GENDER Female Male Count Column N％ Count Column N％ N㈣TAL Single 50 79．4％ 33 89．2％ STATUS Married 13 20．6％ 4 10．8％ Puberty 3 4．8％ 1 2．7％ AGE ONSET Adolescent 28 44．4％ 22 59．5％ Young 16 25．4％ 1 2．7％ adult >25 years 25．4％ 35．1％ PHOTOTYPES II O O．0％ 0 O．0％ III 16 25．40％ 4 10．80％ IV 47 74．60％ 33 89．20％ ETHNICITY Asian 63 l 00％ 37 1 00％ OCCUPATION Student 28 44．4％ 18 48．6％ Employed 30 47．6％ 18 48．6％ Housewife 5 7．9％ 1 2．7％ 3．3．1 Family history of acne There were 1 2 men and 20 women reported to have family history of acne，32 patients in total．Among them，23 patients had ache started at 12—19 years of age (adolescence)，and 9 patients had acne started at or after 20 years of age．Mean age at onset of acne in patients with positive family history was lower than those with negative family history( 1 7．7 VS．1 9．3 years)．The reported acne severity in the family was R 万方数据 兰皇鱼!竺曼坐!!竺堕坚竺塑!里!坐—垦!!竺坠 ranging from mild in 21．9％，moderate in 28．1％，severe in 25％，and subject could not remember for 25％．In our study，positive family history of acne was significantly more frequent in severe acne patients(P<0．05)compared to mild and moderate acne patients． Coefficientsa I Instandardized Standardized Coefficients Coe伍cients Model B Std．Error Beta t Sig． T————————————濡———■—— 一 1 2 ． 61 8 ． 306 8 ． 8． 565 ． 000 FAMILY HISTORY ．．400 ．1 76 一．224 —2．279 。025 a．Dependent Variable：GAGS SEVERITY 3．3．2 History of acne treatment More than half of the subj ects(N=6 1)had been formerly treated for acne；and only(N=3 9)denied preceding treatment。Those stating acne onset at the prepuberty age and the age of 20 or older were also prone to be treatment na'l've(no prior treatment) compared to those with adolescent onset(3．2％VS．45．2％VS．5 1．6％)．Preceding treatments included an extensive selection of systemic and topical medications【With over—the。counter(OTC)selections]。Non—pharmacological treatments such as IPL， red／blue light，and multiple physical treatments(peeling，comedo extraction，and mask) were also reported．Most of the subjects who had previous treatment said that they had at miminum used one topical treatment(prescribed or OTC)．However，maj ority failed to recall their exact previous treatment history；as such，it was not evaluated further．In addition，among those with prior treatments，only 3 7．1％was satisfied with their previous treatment outcome．The level of acne severity in those who had previously treated was higher than those who had no treatment before，although it was statistically insignificant俾>0．05)． 9 万方数据 兰塾鱼!竺墨旦尘!!堡!堡塑竺!竺里竺!! 垦!!塑堕 Coefficientsa Unstandardized Standardized Coefficients Coefficients Model B Std．Error Beta Sig． 1 (Constant) 2．128 ．267 7．983 ．000 PRIOR ．．128 ．．07 1 一．708 ．480 TREATMENT a．Dependent Variable：GAGS SEVERITY 3．4 Clinical Presentation 3．4．1 Ache Severity Global Acne Grading System(GAGS)，as shown in Fig．1，was used to rate acne severity at the study visit．According to its criteria，a total of 3 3 subj ects in this study had mild acne(women 8 1．8％，men 1 8．2％)，47 had moderate acne(women 59．6％，men 40．4％)， 1 2 had severe acne(women 50％，men 50％)，and 8 had very severe acne (women 25％，men 75％)．It is shown that frequency of women with mild and moderate acne was twice as much as men，on the other hand，twice as many men as women had severe to very severe acne．However，it should be remembered that relationship between acne severity and gender was not assessed in this study．In addition，among 3 8 subj ects who denied previous treatment，39．5％had mild acne，44．7％had moderate acne and 1 5．8％had severe or very severe acne(Table 4)．Common presentations of acne among each level of severity in this study were shown in front view pictures taken with VISIA (Fig．3 to Fig．6．)． 10 万方数据 Zhejiang University Master Thesis Results SEVERITY ●口口● 麴一 旺 Figure 1 Global acne grading system at visit． Figure 3 Visia picture of mild acne Figure 4 Visia picture of moderate acne 万方数据 Zhejiang University Master Thesis Results Figure 5 Visia picture of severe acne Figure 6 Visia picture of very severe aCne 3．4．2 Distribution and Location of acne lesions Majority of the subjects in this study(92％)presented with mixed ache that consists of both inflammatory(papules，pustules)and non-inflammatory lesions(open or closed comedones)．Another 3％presented with both mixed acne lesions and nodules，while the rest had either inflammatory or non-inflammatory lesions only． Areas of the face presented with acne lesions were measured．As seen in Fig．2， nearly equal percentage of subjects had comedonal lesions on the forehead，mandible， and cheeks．Inflammatory lesions of both men and women were seen the most on the right cheek and mandibular area，1ess on the left cheek and forehead，and the 1east on temples．Left cheek and mandible area were place mostly seen among 3％subjects with nodules；however，lesions were not found on temples． 1 2 万方数据 Zhejiang University Master Thesis Results Figure 2 Distribution of acne lesions by facial zone for the group overall，reported as the percentage of patients with lesions in that zone Forehead Comedones 87％ Temples Inflammatory 62％ Comedones 45％ Nodules 1％ Inflammatory 28％ Nodules 0％ Left Cheek Comedones 89％ Inflammatory 66％ Nodules 3％ Right Cheek Comedones 89％ Mandible Inflammatory 80％ Comedones 84％ Nodules 1％ Inflammatory 83％ Nodules 3％ 3。4．3 Back body involvement Acne involvements on the back body area were reported by a total of 37 subjects (40．5％men，59．5％women)．Among them，most subjects had moderate acne(48．6％) followed by very severe acne(1 9％)，then mild and severe acne(1 6．2％each)．In addition，the lesions presented on this area were also more likely to be mixed acne 1esjons 3．5 Additional clinical features 3．5．1 Erythema Limited only on the area of the face，erythema was seen among two third of the subjects(N=76)，which occurred in 42．1％of men and 57．9％of women(Table 2)． Erythema was most commonly found on the mandible area followed by cheeks then temples and forehead．In this study,we identified that men and women in adulthood had the tendency to have erythema compared to those of adolescent age and younger．It was appeared with declining frequency in groups of older age and most frequently seen in 13 万方数据 Zhejiang University Master Thesis Resuhs subjects of 20-25 years old． 3．5．2 Hyperseborrhoea Based on our observation，hyperseborrhoea was seen in 76 subjects(Table 2)． Among those subjects，both men and women tended tO have moderate acne(54．8％men， 55．6％womenl followed by severe to very severe acne in 35．5％men and mild acne in 26．7％women．Other 1 7．7％of women with hyperserborrhoea reported to have severe to very severe acne，while the least was found in men with mild acne．In addition，only about half of subj ects with hyperseborrhoea seemed to have acne lesions on the back body area． 3．5．3 Scars From the data presented(Table 2)，we could see that acne scars—mainly atrophic were seen in 77％of the subjects．It is shown that men and women with mixed acne lesions were more likely to have acne scars rather than others．Though it should be noted that there were very slight numbers of patients with either inflammatory(N=2) or non—inflammatory CN 2)lesions only．Similar to PIH and erythema，subj ects presented with scars were mostly seen in age 20—25 years old(53．2％1 followed by age 26 or older(32．5％)，and adolescents(14_3％)．in both men and women，scars were presented mostly on the cheeks(76．6％on both right and left cheek)，followed by temples(men 28．6％，women 20．8％)，mandibular area(men 33．8％，women 23．4％)， and forehead(men 1 5．6％，women 6．5％)．A very small percentage of those with scars (9．1％)一mainly men—had both atrophic and hypertrophic scars，which mostly located on the mandibular area 】4 万方数据 Zhejiang University Master Thesis Table 2 Erythema，hyperseborrhoea and scars GENDER Male Female Column Column Count Count N％ N％ Yes 31 83．78％ 45 71．43％ HYPERSEBORR HEA No 6 16．22％ 18 28．57％ ERYTHEMA Yes 32 86．49％ 43 68．25％ No 5 13．51％ 20 31．75％ Error 0 0．00％ 0 0．00％ SCARS YeS 35 94．59％ 42 66．67％ No 2 5．41％ 21 33．33％ Error 0 0．00％ 0 O．00％ TYPE OF SCARS Atrophic 30 8 1．08％40 63．49％ Hypenrophic 0 0．00％ 0 0．oo％ Both hypemophjc 5 13．51％ 2 3．17％ and atrophic 万方数据 Zhejiang University Master Thesis 3．5．4 Post-inflammatory hyperpigmentation As presented in Table 3，PIH was seen in the greater number of subj ects in this study．Facial areas frequently seen with PIH 1esions in both men and women were mandible area，followed by cheeks，forehead，and temples．Accordingly，PIH lesion was found mostly in adulthood subjects谢th 20一25 years of age(5 1．1％)，fewer in age 26 or older(34％)，and least among adolescents(14．9％)．However，it should be remembered that there were small number of adolescent patients participated in the study．Among those 5 1．1％subjects，20．8％had mild acne，52．1％had moderate acne，and the rest had severe to very severe acne．There were 72 of subj ects presented with both PIH and erythema． Table 3 Distribution of PIH GENDER Male Female ColumnN Colunm Count Count ％ N％ Forehead PIH Yes 如 81．08％ 32 50．79％ No 7 18．92％ 31 49．21％ Yes " 45．95％ 17 26。98％ Template PIH No 加 54．05％ 46 73．02％ Righ t — Yes 勰 75．68％ 44 69．84％ Areas PIH Cheek No 9 24．32％ 19 30．16％ Yes 抄 78．38％ 45 71．43％ Left Cheek PIH No 8 21．62％ 18 28．57％ Yes 驺 89．19％ 51 80．95％ PIH Mandibular No 4 10．81％ 12 19．05％ 万方数据 Zhejiang University Master Thesis Results 3．5．5 Menstrual Cycle Regular menstrual cycle was reported by majority of women in this study．Age of menstruation onset and duration of menstruation cycles were not included in this study， therefore it was not analyzed further．On the other hand，irregular menstrual cycle was reported only by 1 7．5％of women in this study with the majority of those aged 20 years old and older．However，among those with irregular menstrual cycles，only 1 woman identified to have hirsutism，and none for other endocrine abnormality． In addition，women believed that menstrual cycles were related晰th acne worsening，stating that most frequently acne flares occurred before onset of menses but also after and during for small numbers of women． 3．6 Behaviors and lifestyle factors According to Chi-square test and cross—table test，it was observed that the P value for prior treatment，family history，behaviors and lifestyle factors(alcohol intake， cigarettes smoking，constipation，insomnia，occupational chemical exposure，physical activity and exercise，skincare and use of cosmetics)were all larger than 0．05 indicating that the spread of the indicators listed are not independent significantly at level of O．05 (Table 4、．The results identified the fact that there might be no correlation between above mentioned factors and the levels of severity．In addition，dietary intake，daily stress and j ob stress was assessed separately from the other factors． According to regression analysis，taking all factors into consideration as independent variables，the level of severity as dependent variable，it was observed that only the factors of moisturizer had significant estimation of coefficient in the model， which indicates the fact that the influence of moisturizer to the level of severity is significant，where the relationship is positive． 17 万方数据 ∞=j∞o醴 N Q 睁o ， ， o o o o o r分 ∞争 旧寸o L．∞．o 西N．o NN．0 ‘o o a) o 高∞．r 石兰 N∞卜∞ nN卜-￡ ∞∞N．8 -luo mLm3口∞ 拳零 ∞∞ N卜 Co n 零。．DN 零o．崎卜 摹崎．N1． 零田．卜∞ 摹o．o崎 零o．o∞ 墨o．o 暴o．gN 零o．旧卜 零o．o 零o．ool， 紧旧．卜n 摹崎．卜n 零o．∞N 山叱山>山∞卜芷山> 峨 t"q co r卜 寸 寸 o N co o∞ n ∞ 零卜。。 永n．n∞ 墨卜ol， 暴n．n∞ 摹o．o 暴o．oor 摹o．o的 墨o．o崎 零o．o 墨o．o∞ 墨o．oD 摹o．o 墨o．001． 零o．o心 术卜r寸 暴∞．∞ 山叱山>山∽ ∞ 寸 N oI． o NI， ‘o co o cD co o Nr ∞ ∞ I}一叱山>山∞ 摹∞．n。 摹州∞∞ 零寸nN 零o．o卜 零∞．01． 零冀西∞ 摹∞．@寸 暴o．∞寸 墨n．寸 墨西．鬲 摹■∞∞ 9乞n．寸 零卜∞西 零西．寸I． 零L_∞o 尜o．卜r 山J_《芷山Qo芝 。n 卜I， = on ∞ N寸 NN nN N 崎L． Nn N 。寸 卜 Nn ∞ ∞g一京矗op日蠹∞Jo芑矗。一扫∞9J一一，扫一矗≯o∽o口o《寸o_盆矗一 零啦．寸D 暴D6寸 墨r．Nl， 暴o．卜∞ 尜L．西 零o．oo 尜∞．no 零n．卜N 尜L．o 墨寸N寸 零∞．卜田 文L．NP 摹西．卜∞ 零n．卜N 零o．卜旧 零N．∞l- oJ一乏 ∞1． 吣I． 寸 西N ∞ on PN 寸l_ or 寸 ①N o or 田Dx oc ∞∞x oc ∞∞x oc ∞∞x o亡 ∞∞x oc co￡o c∞《o ∞∞E；oEo田 ∞∞LIJI—oEo∞ k∞>∞c、rco口一∞∞ ．I∞>∞c、I．coD一∞∞ ∞一∞Q丘一J。葚苫参一∞J3AI簋3 叱。匣正 _10工oo_1< o圣>{o乏∞ Vlz芝o∞圣 J《o一芝山工o 山匝]∞o正×山 J《o一∞卜工正 ℃}一>一J-o< 山∞一。叱山v^山 _LZ山主_L《山世_L zo一．I_V正一卜∞zoo M趸雷二N 万方数据 碑=T1∞∞g o o o o o no．o 1．o．o o■o 卜n．o 寸o．o 崎ro．寸r 。曲o．卜r 崎寸N．西 卜旧L．n 寸寸④．Nr 零o．o 零o．001． 尜o．o 暴o。oD 零协．卜∞ 暴田．Nr 零o．ooI． 墨o．o 零o．o 墨o．oor 墨旧．N【． 摹n．卜∞ 暴旧．卜n 暴田．No 0 ∞0 寸 n r ∞ o o ∞ r卜 n∞ 摹n．∞∞ 零n．nn 摹n．∞n 暴卜I．寸 零卜olr 尜卜1．寸 零o．田卜 零卜．or 零n．∞ 幂o．oor 暴o．田N 暴o．崎卜 墨∞．∞啦 零卜r寸 寸 寸 寸 ∞ N ∞ a) N Nl- n o) 卜∞ 尜D．∞ 零崎．旧N 零∞．寸卜 零o．寸∞ 零o．oo 零卜∞卜 墨∞．N1． 零吣．田N 零卜．寸寸 零∞．∞N 暴N．n崎 零N．∞n 零∞．oI． 墨o．oor N 寸 卜n ∞ Nr I_N 寸I． 田N 卜r 卜寸 L． Dn or 工．n 墨r．Nr 零∞．崎卜 摹L．Nr 摹1．o 墨∞．卜N 紧o．no 零曲．寸∞ 摹n．卜N 零N．∞P 零o．001． 零冀西∞ 墨o，o∞ 零叫∞I_ 器∞．L8 寸 ∞N 寸 ∞ rN ∞I． 西 nn nr oN o 卜N ∞ox oC ∞∞x oc 亡o《o 匕∞#o 匕o#o ∞oE|1∞Eo∞ ∞ouJIloLl_Io田 ∞oE|loEo∞ o_Lo±o∞ ．Io>o匕、I-co口一∞∞ Lo>∞c、Eo口一∞∞ L∞>∞u，Eoala∞ 工∞VM z3∽ >]l苫0．05)． Coefficients8 Unstandardized Standardized Coe伍cients Coefficients Sig． Model B Std．Error Beta 1 fConstant) 2．297 ．41 6 5．5 1 8 ．000 ALCOHO 一．192 ．225 一．086 -．853 ．396 L a．Dependent Variable：GAGS SEVERITY 3．6．2 Cigarette smoking Nine subjects in this study reported smoking(8 men，1 women)．Among those men， 50％had moderate acne，25％each had mild and severe to very severe acne，while the only woman reported smoking had mild acne．Severity of acne was similar regardless cigarette smoking，however there was a positive relationship between the level of acne severity and smoking(insignificant，P>O．05) Coefficients3 Unstandardized Standardized Coefficients Coefficients Sig Model B Std．Error Beta 1 (Constant) 1．822 ．597 3．05 1 ．003 SMOKIN ．067 ．309 ．022 ．2 1 7 ．828 G a．Dependent Variable：GAGS SEVERITY 3．6．3 Constipation 42％subjects(57．1％women，42．9％men)in this study reported to have constipation sometimes．53％subjects(64．2％women，35．8％men)reported to seldom／never have constipation，while only 5％(only women)reported to often have 22 万方数据 constipation．Acne severity was the same among those who often，sometimes，and seldom／never have constipation(P>0．05)，even though there was a positive relationship． Coefficients8 Unstandardized Standardized Coefficients Coef![icients Model B Std．Error Beta Sig． 1 (Constant) 1．880 ．244 7．707 ．000 CONSTIPATION ．046 ．1 50 ．03 1 ．3 06 ．760 a．Dependent Variable：GAGS SEVERITY 3．6．4 Sleep quality 37％subjects in the study，which consisted of 59．5％men and 40．5％women， reported trouble of sleeping or insomnia．Moderate acne(40．5％)was identified the most among them，which then followed by mild acne(3 7．8％)，and the rest in severe to very severe acne．As seen，there was positive relationship between the level of acne severity and insomnia．However，it was not statistically significant(P>0．05)． Coefficients8 Unstandardized Standardized Coefficients Coefficients Model B Std．Error Beta Sig． INSOMNIA ．092 ．183 。05l 。504 ．615 a．Dependent Variable：GAGS SEVERITY 23 万方数据 Zhejiang University Master Thesis Results 3．6．5 Occupational chemical exposure Occupational chemical exposure was mentioned only in a very small numbers of subjects(6％)．Among these，67％had moderate acne and 33．3％had mild acne．It can be seen that there was a positive relationship between acne severity and occupational chemical exposure，although not statistically significant(P>0．05)． Coefficients8 Standardize Unstandardized d Coefficients Coefficients Model B Std．Error Beta Sig． 1(Constant) ．677 ．717 ．945 ．347 CHEMICAL ．656 。367 ．178 1．789 ．077 EXPOSUI己E a．Dependent Variable：GAGS SEVERITY 3．6．6 Physical activity and exercise Ma j ority of the subj ects in this group stated that some exercise or physical activity was a part of their day-to—day routine at best．Only a small number of subj ects(25％) reported to seldom exercise．Negative relationship between acne severity and exercise was present，which indicated that the less exercise they have the more severe acne they would have．Yet，it was statistically insignificant(P>0．05)． 24 万方数据 Zhejiang University Master Thesis Results Coeffidents8 Standardize Unstandardized d Coefficients Coefficients Model B Std．Error Beta Sig． 1(Constant) 2．114 。280 7．539 ．000 PHYSICAL ．．086 ．139 一．062 ．．616 ．539 ACTⅣITY EXERCISE a．Dependent Variable：GAGS SEVERITY 3．6．7 Sun exposure A total of 80％subj ects in this study reported to sometimes or often have sun exposure daily．There was higher amount of subjects wim severe and very severe acne amongst them compared to those with seldom sun exposure daily(80％Vs．20％)．The linear equation coefficient table indicates positive relationship between the level of acne severity and sun exposure also supported this result．Nevertheless，it was not statistically significant(P>0．05)，which means that sun exposure had no relationship with acne severity． Coefficients8 Unstandardized Standardized Coefficients Coefficients Model B Std．Error Beta Sig． 1(Constant) 1．942 ．362 5．368 ．000 SUN ．004 ．174 ．002 ．022 ．982 EXPOSURE a．Dependent Variable：GAGS SEVERITY 25 万方数据 3．6．8 Skin care and use of cosmetics Skincare products assessed in this study were moisturizer，facial wash(OTC／ prescribed)，and sunscreen．In describing the use of facial wash，all of the subj ects reported to use OTC and none reported prescribed facial wash．Thus，it was not analyzed further． Less than half of the subj ects in this study only reported the use of sunscreen，while 60％subj ects reported to seldom／never use sunscreen on their daily life．There was negative relationship between the level of acne severity and sunscreen use．This relationship was supported by significantly greater number of subj ects with severe to very severe acne among non—daily sunscreen users compared with dally sunscreen users (85％VS．1 5％，P<0．05)．There were 24％subjects reported to seldom／never use moisturizer on daily basis．The fact of negative relationship between the level of acne severity and moisturizer use was found，indicating that acne severity will increase谢th decrease or absent use of moisturizer．W汕P0．05)． 26 万方数据 Zhejiang University Master Th——esis Coefficients8 Unstandardized Standardized Coefficients Coefficients Model B Std．Error Beta t Sig． 1(Constant) 2．397 ．206 11．653 ．000 SUNSCREE ．．294 ．123 ．．235 ．2．392 ．019 N a。Dependent Variable：GAGS Coefficients8 a．Dependent Variable：GAGS SEVERITY Coefficients8 Unstandardized Standardized Coe伍cients Coefficients Model B Std．Error Beta t Sig． 1 (Constant) 1．406 ．340 4．131 ．000 COSMETIC ．318 ．192 ．165 1．654 ．101 a。Dependent Variable：GAGS SEVERITY 27 万方数据 Zhejiang University Master Thesis 3．6．9 Daily stress and j ob stress On a range of 1 0，the mean rating of reported day-to-day stress was 3．64，which could imply that the stress rating among overall subjects in this study was mild．Mean daily stress rating among each level of acne severity was also calculated(Table 5)．As seen，the higher the daily stress was，the higher the level of acne severity would be．On the contrary，daily stress may be just one of the influencing factors to a very severe acne． However，that Was not statistically significant(P>0．05)，indicating no correlation of daily stress、vith the level of acne severity． Employed subj ects were questioned if they felt the j obs they had were psychologically or physically stressful．A total of 3 1．25％stated that their jobs were stressful physically while 68．75％stated that their jobs were stressful psych0109ically (Table 5)．It was found that subjects谢th psychological stress job were linked with more severe acne compared to those with physical stress job(75％VS．25％)． Table 5 Daily stress and job stress DAILYSTRES Mean 3．39 3．57 4．25 4．13 S Standard Deviation 2．22 2．05 2．01 1．36 JOBSTRESS physical Count 3 10 1 1 ColumnN 20．0％40．0％ 20．0％ 33．3％ ％ psychology Count 12 15 4 2 ColumnN 80．0％ 60．0％ 80．0％ 66．7％ ％ 28 万方数据 圣垫笪!塑曼坐!!!堡堕坚竺!竺里竺堡 垦!!竺!堕 DAILYSTRES S SEVERITY DAILYSTRESS Pearson Correlation 1 ．1 3 0 叭 ～ 由 脚 鳃 N ∞ m ∞ E V E 对 T Y 蚍 一 撕 叽 如 。 。 叭 ～ D 粥 一 — — 一 一 — 一 N 一 一 一 ∞一 m 一 ∞一 Coefficients8 Unstandardized Standardized Coefficients Coefficients Model B Std．Error Beta Sig． 1 (Constant) 1．748 ．1 79 9．744 ．000 DAILY ．056 ．043 ．130 1．295 ．198 STRESS a．Dependent Variable：SEVERITY 3．6．10 Dietary Intake The majority of the subjects reported consumption of dairy products，followed by sweet foods，oily foods，spicy foods and other respectively(Table 6)．It should be noted that correlation of other foods such as clear foods and seafood consumption with acne severity was not further assessed． Moderate to very severe acne was mostly seen among those with dietary intake compared to those without(59．7％VS．40．3％)．Nevertheless，regression analysis showed that no meaningful association between severity of acne and dairy intake rP>0．05)． Sweet foods were consumed by half of the subjects in this study．Though there were positive correlation indicating that increase amount of sweet foods consumption 29 万方数据 will also increase the level of acne severity，acne severity was comparable among those with and without high sugar content foods intake(P>O．05)． Oily foods consumption was reported by 3 9％of subj ects．Among them，maj ority presented with moderate acne．However，there was no significantly difference in acne severity among those who consumed and did not consume oily foods(P>0．05)． Approximately one third of the subj ects in this study reported spicy foods consumption．There was an estimation indicating that if a person consumed spicy foods， the severity of acne will also increase．Yet，it was not statistically significant(P>0．05)， similar acne severity regardless of spicy foods． 30 万方数据 N fT 屺 o 心寸．o 卜o．0 1．0 nN．0 ⑦N．0 ● 1【屿■H 寸⑦n．N ∞一一 寸寸n 卜N一．寸 卜n卜．n ∞1Ij舀g o高T1∥∞土I：『J 装o．on 摹o．on 装■卜n 装■N心 装■N一 寒■卜∞ 心卧价．卜n 摹■N屺 装■㈧H 零n卜∞ 装o．o 摹o．00_【 o比gIIoo宕阻 叫幺叫>∞∽净醴叫> 寸 寸 n n H 卜 n n H 卜 o ∞ ≯o口oj口o-I■ 装o．0n 装o．0n 装o“N 装o“卜 装■H寸 装C．∞n 装010n 装o．0n 装o．0 摹o．00一 装c．∞ 装●一心 o泓g口ooB乱 ∞醒∞>叫∽ ∞ 也 n ⑦ ∽ 卜 ∞ ∞ o 型 H ≯o口oj口o-■ 净h11凹幽>叫∽ 装寸．卜n 装岫．N寸 摹D．N寸 装寸．卜n 摹I．一n 装@．∞寸 装o．屺。 摹o．寸n 装C．寸 装卜塞 摹o．o 装o．00_【 ∞量基皇一声瓮苗“盆婚oIq畏一 o乩日菪oo矗乱 衄一<配∞Qoq艺 卜N oN oN 卜N 寸N nN 一n 屺1【 t"q 导。 卜寸 ≯o岛oj口o-I o 装寸．N寸 装心．卜n 摹C．卜N 装●N卜 装C．卜N 装●N卜 零节N寸 摹心．卜n 摹o．o 装o．00一 摹o．C 装。一① o缸旦《oo矗阻 QrIHq二 = S ⑦ 葛 ① 寸t"q 要 金 。 罱一 t"q n ≯oIIoj口o．I■ z—zo上L1。ko一∞日芝》1I∞-Io>一LI ∞o≯ ∽o≯ 。g ∽o≯ ∞o≯ cc ∽o≯ 。【I ∽o≯ oZ r__1吐c日!【u LIN 一叫叫|／嗲∽ ∽Qoo皿 净UH厶∽ ∽Qoo日 净■Ho ∽Qoo日 净配H0．05)． According to one—way ANOVA analysis，the mean values for emotional scale of Skindex．29 deviated from each other at level of 0．05 within the group level of severity． The LSD test showed the fact that people with very severe acne has the highest score of emotional scales of Skindex．29． 33 万方数据 Zhejiang University Master Thesis Resuits Coefficients8 Unstandardized Standardized Coefficients Coefficients Model B Std．Error Beta t Sig． 1 (Constant) 31．074 1．957 15．881 ．000 GAGS ．259 ．915 ．029 ．283 ．778 a。Dependent Variable：SKINDEX 29 SCORE Correlations SKINDEX SCOI己E GAGS EMOTIONAL SCALE Pearson Correlation 1 ．029 SKINDEX．29 Sig．(2-tailed) ．778 N 100 100 GAGS Pearson Correlation ．029 1 Sig．(2-tailed) ．778 N 100 100 ______l____________---__________---_______-____-_________-_●-____-______●-●___●-_一●_●-__-___●●______■_______●__-___-_-__-___●_--_-__ ANoVA SKINDEX 29 SCORE Sum of Squares df Mean Square F Sig． Between Groups 1 44．1 99 3 48．066 ．749 ．526 Within Groups 6162．161 96 64．189 Total 6306．360 99 34 万方数据 Zhejiang University Master Thesis Results Multiple Comparisons Dependent Variable：SKINDEX 29 SCORE LSD mild moderate 1．14249 1．81958 ．532 ．2．4693 4．7543 SeVere 1．95455 2．70078 ．47 1 —3．4065 7．3156 very —2．87879 3．15734 ．364 ．9．1461 3．3885 SeVere moderate mild —1．14249 1．81958 ．532 —4．7543 2．4693 SeVere ．81206 2．59130 ．755 —4．3316 5．9557 very —4．02128 3．06421 ．193 。10．1037 2．0611 seVere severe mild —1．95455 2．70078 ．471 ．7．3156 3．4065 moderate 一．81206 2．59130 ．755 —5．9557 4．3316 very ．4．83333 3．65688 ．189 —12．0922 2．4255 SeVere very mild 2．87879 3．15734 ．364 ．3．3885 9．1461 severe moderate 4．02128 3．06421 ．193 ．2．0611 10．1037 SeVere 4．83333 3．65688 ．189 —2．4255 12．0922 35 万方数据 Zhejiang University Master Thesis Discussion 4．Discussion Acne is a cutaneous disorder，a multifactorial pathogenesis inflammation that comprising the pilosebaceous unit．Pleomorphic lesion is the typical aspect of acne， alongside with simultaneously present different lesions in equivalent patient：both inflammatory lesions as papules and pustules and non—inflammatory lesions as comedones．Nodule，cyst，scars and draining sinuses could be existent in severe acne as well．Acne presented in a wide variety of forms depending on the number，type，and severity of the predominant lesion regarding this reason．[241 Then again，as a result of different genetic background and lifestyle factors，the risk factors and prevalence of acne are not likely to be consistent，and the application of various treatments also differs in each ache patients．Therefore，this study assesses the clinical manifestation and characteristics associated with acne in patients thoroughly． Our study included 1 00 subjects covering all age groups．Compatible to Shen，et a1． [2引，we found that men were predominant in adolescent acne，while women were predominant in adult ache．This is also comparable with UK piloted two studies，[26,27] which showed that acne was hardly seen in people with age over 50，which is somewhat unalike from Schafer et a1．[28]who discovered that in Gerrnans with age over 59．the acne incidence was as great as 1 3％． Furthermore we discovered that 46％of the total acne subjects was accounted with adult acne，and that most adult acne cases are persistent acne．Though acne in adulthood has formerly been analyzed【27·3 11．a small number of studies have examined the disparities between persistent acne and late onset ache．We established that halfof those with adult onset had a milder ache severity．Both men and women were evenly affected in persistent acne，whereas women were predominant in late onset acne．Nonetheless，it should be distinguished that the total of women patients included in the study were twice as many as men patients． Proposition that acne in adults differs from that in adolescents has been made，in which adult acne as developing more inflammatory lesions although less lesions overall； as developing deep—seated，long—lasting papules，nodules or cysts(in few numbers 36 万方数据 圣!鱼!竺曼旦璺i!!堡!堡坚型!!!!竺!! 里!!!旦!堕旦璺 generally)with inflammatory flares；and as mandibular area localization of lesions．吲 In this study，these clinical presentations were found，not only in adult patients but also in all patients of acne．Mixed acne lesions were present in maj ority of the subj ects， while only 3％subjects were seen with nodules and cysts． Only 37％subjects in the study reported involvement of acne on non-facial skin area．Dependable with Faure M，et a1．[331 we discovered that those with back body involvement were more likely to have very severe cone on the face，although higher severity scores were given as the back body was involved． According to Global Acne Grading Score，47％of subjects had moderate acne， followed by mild acne(33％)，severe acne(12％)and very severe acne(8％)． Nevertheless，it should be remembered that patients were sequentially registered at our dermatologists’outpatient clinic and there was no necessity of study enrollment to be the first visit for acne．Beyond half subjects(6 1％)informed using some kind of treatments for acne at the time capturing the data，yet they kept disturbed by their acne to continue consulting the dermatologist． Adolescent acne and adult acne patients were equally to be previously treated．We reasoned that the increasing population of patients in dermatology clinics might be at least somewhat attributable to patients old enough to be‘‘better acknowledged with the aVailable remedies and less forbearing their condition”．[321 Opposed to a recent article， we found no significant association between the level of acne severity and history of prior treatment．【33】 Up to this time several evidence showing acne is a hereditary disease has been established．Xu et a1．【35】stated that hereditary factors are essential in regulating individual susceptibility to acne vulgaris in Chinese patients．Though Our study design does not let US to pull any assumption regarding a potential genetics contribution to acne， deliberating the work of prior studies，[74,751 we nevertheless are able to conclude that hereditary factors play a vital role in the etiology and pathogenesis of acne vulgaris in (hinese patients．A matter of fact，related to Evans et a1．【34】Our study also enhanced that a positive family history is significantly correlated with advanced risk of developing more severe acne． Likewise，consistent with other literature，[34]Our study illustrates that patients with 万方数据 兰皇笪!塑曼旦兰!∑!!里堕坚型竺婴!坐 里!!!竺!!!竺 positive family history had earlier onset of acne as well．Significantly greater percentage of subjects with early onset acne had familial acne history(71．9％in the early onset group VS．28．1％in the late onset group)，which indicates that hereditary factors play all essential part in early onset acne and that late onset acne is more affected by acquired factors，such as hormone dysregulation，lifestyle factors，and environmental effects． Scarring appears in 95％patients wim acne and in both sexes evenly as indicated in a literature．冈Alternatively，just half of the subjects in a Hong Kong based prevalence study of acne developed post inflammatory hyperpigmentation．[371 Our finding was consistent with the literatures，with scarring in 87％．However，PIH Was not found in half of subjects in this study，but the majority of them(94％)．PIH severity is associated to the inflammation degree that may be caused by endogenous inflammatory skin disorders．[381 As shown，majority of the patients in this study had moderate to very severe acne；thus，our finding might fluctuate from the presented literature．One theory to describe the scars frequency in subj ects between 20—25 years old could be that inflammatory acne is frequently more severe among them compared to others，and this inflammation increased could be more often related with scarring that resolve in years． Erythema Was universal and was described in 75％of subjects．As some patients were using some kind of treatment at the time capturing the data，PIH and erythema rates may perhaps be higher．[39】 Williams and Cunliffe have declared that in 60—70％of women acne worsens premenstrually．[401 Premenstrual acne flare reported at rate of 27％in a sample of 85 women by Shaw．[411 Similar to Our finding in which there was 50．8％women reported premenstrual acne flares．Even if a hypothesis about changes of surface lipid composition in premenstrual phase，the changes in hydration of the molecular structure of keratins，[421 or prostaglandin effects through its vasoactive properties is present，[43】 the accurate cause for this flare up is yet not found． Acne progression changes have been suggested to relate with number of factors such as lifestyle factors and stress．Worsening of acne as a result of psychological stress was reported in 80％of acne patients in a Korean study【44】and 50％of female acne patients in a French study．[311 In this current study，68．75％of subjects reported that job stress was associated with acne．Stress is accused for causing flare—ups over and over 38 万方数据 垫鱼!竺曼坐堡!望堕坚竺!竺堡!堑! 堡!!兰!堕竺 again．Flare-ups are frequently reported while they are under a lot of pressure and stress． There is a theory stating that adult female ache is connected to cllromc stress，which raises the adrenal androgens secretion and results in hyperplasia of the sebaceous gland and subsequent comedones production．[451 This theory is strengthened by the correlation observed between level of emotional stress and elevated serum cortisol levels in acne patients．[46-48]Besides，insomnia or poor sleep quality might act out as a stressor promoting secretion hormones of stress and affecting immune system．Those 1] stress homones could haye some bearing on acne development and severity．[49-5 Associations between lifestyle factors，for example smoking and drinking have shown collj[1icting resuIts on previous studies．[52-56]Alcohol is believed to induce recruitment of the inflammatory cell and vascular ectasia，which then aggravates acne． Even though a higher prevalence of smokers and drinkers among adults was indicated in our study，no affirmatory association between drinking／smoking and acne Can be recognized as some individuals might start to drink or smoke regarding onset of acne or even as a consequence．A latest study【5 7】informed a dose—dependent inverse correlation between occurrence of severe acne and day—to—day cigarette intake．In spite of that， comprehensive data concerning cigarette intake were not explored throughout Our study； therefore，the analysis of the correlation among acne severity and the quantity of cigarette smoking is limited． Exercise is considered to affect acne patients in two ways．The first one is that exercise accelerates blood flow，which nourishes the skin and aid to keep acne under contr01．Nonetheless，forceful exercise triggers sweating and perspiration，which unclogs the pores with bacteria and at last leading to acne．In the present study，no association between acne severity and physical activity／exercise was found． Zhang H et a1．[761 discovered that dysfunctional gastrointestinal tract is a principal risk factor for diseases of sebaceous gland and is tied with their development and occurrence．Gastrointestinal dysfunction may disturb the minor elements absorption， such as zinc，copper and others；it may also increase sebaceous secretion and the proliferation of lipophilic Malassezia．It is acknowledged that immunological fimction reduction，epithelial lipid metabolism and hyperkeratosis impairment is associated with a decreased zinc concentration in the body．Hence，keratin barrier function becomes 39 万方数据 Zhejiang University Master Thesis Discussion impaired and facilitates the formation of greasy scale，pre—existing sebaceous gland diseases worsening．[59,77,78]However，we found no association between constipation and acne． Evidence proposes that typical foods and food substances may indirectly or even directly impact the steroid hormones inflammation and balance，follicular keratinocyte proliferation and differentiation，and hence synthesis of sebum．These three fundamental physiologic mechanisms dysregulation alongside propionibacterium acne involvement signifies the cause known for acne．[60’61】One of the questions that were focused in this study was raised from patients’general faith that spicy or salty foods may lead to more severe acne．However，it has rarely been mentioned in the literatures．In the present study，we found that neither salty nor spicy foods is connected to severity of acne， which suitable with the recent literature written bv E1 Darouti MA et a1．[62] Dietary factors(chocolate，oily and fatty foods，and high sugar content foods)were identified as worsening factors of acne by almost half of the Australian medical students in a Green and Sinclair study．【631 On the contrary，there was no relationship found between consumption of high sugar content foods or dairy products and acne severity in our study that is consistent with the studv of FuIton et a1．。[64】who determined that wide． ranging dietary were not related to acne severity．Lately，however，dietary factors，such as dairy intake or high glycemic load have been suggested by several studies to play a part in the pathogenesis of acne．[651 Fascinatingly，Adebamowo et a1．【66．68】discovered a relationship between acne and milk intake in adolescents，which may be associated wim hormonal and metabolic factors in milk．At a cellular level，high intake of dairy is believed to promote acne pathogenesis by providing exogenous hormones and stimulating pathways that converge with the effects of insulin on the PSU．[85,86]To Our knowledge，there have not been any studies that indicate a higher rate of dairy consumption among the late adolescent period；yet，谢th the popularity of breakfast cereals，cheese，buRer，chocolate milk，ice cream，and powdered whey proteins among this population，it is easy to contemplate how such relationship could be made． Amino acids，primarily leucine，initiated from dairy milk and whey directly stimulate the L—type amino acid transporter(LAT)originated in sebaceous cells and keratinocytes，signaling a cascade of downstream signaling events that lead to activation 40 万方数据 Zhejiang University Master Thesis Discussion of mTORC 1，independent of the Akt signaling pathway．[87】This protein is thought to control the lipogenesis and protein synthesis that drive sebaceous activity and ductal plugging，respectively．【86】Apart from amino acids，(cow)milk is also known to contain exogenous steroid hormones that are true anabolic androgen precursors of DHT， including 5a—pregnanedoine，5a—pregnan一3B—ol一20一one，5a—androstene一3B，1 7B-diol，5a— androstanedoin，and 5a．androstaJl．3B．01．17一one．[88,89]At this time，it is unknown whether these particular molecules share activating capabilities similar tO DHT； however，their presence increases the amount of substrate available for 5a—reductase that， in tl】m，can produce more DHT．[901 The glycemic index is merely an assigned number to any effect of a certain food on an individual，s level of blood glucose，typically ranging between 50 and 1 00．【86，87】High glycemic index foods(>70)，including glucose，white rice，white bread，and chocolate， stimulate the release of insulin from beta cells of the pancreas．Insulin activates the Akt signaling pathway directly through its receptor and indirectly through the production of IGF．1 and its receptor．[85,86]The effect of IGF一1 on the cells of the PSU is two．pronged： either stimulating enzymes taking part in stepwise DHT synthesis pathway or directly activating its receptor(IGF一1 R)on the cells．The final pathway will unite with the downstream signaling events of the insulin receptor，binding to and activating the protein kinase Akt．[85]In nucleus，Akt Call then phosphorylate its target，FoxO 1，and inactivate it．[851 FoxO 1 deactivation leaves the androgen receptor，a highly active and vulnerable target during late adolescence，free to stimulate the necessary gene transcription that drives the keratinocytes proliferation． Maj ority of women in this study reported using cosmetic products to cover acne， pigmentation and scarring．A questionnaire—based study conducted by Dreno B et a1．【69】 discovered that acne severity is correlated to the use of cosmetics．Though we believe that cosmetics Can be a factor in acne when abundant and specifically localized closed comedones on the cheeks and forehead，the same result was not achieved in OUr study． Diverse acne treatments offer different action modes，but all aim to target the four aspects of acne pathology。Topical acne medications often contribute to skin dryness． Likewise，the most effective medication for acne，oral isotretinoin，generally causes cheilitis，dries skin，and photosensitivity．[701 Barrier disruption of the stratum comeum 万方数据 Zhejiang University Master Thesis Discussion may be caused by dryness or skin irritation，which then leads to increase trans- epidermal water loss(TEWL)and production of inflammation．[711 Hence，moisturizers can independently contribute in improving signs and symptoms of acne．【70】In agreement，we postulated that moisturizer is related to acne severity，indicating that the decreased amount of moisturizer use will increase acne severity． Acne has shown to be improved by natural sunlight；however，acne and other facial scars frequently show enhanced photo—aging agents，whereas some oral and many topical treatments for acne might be photosensitizing．Therefore，excellent UVA protection is required in an acne-affected skin to avoid recently healed acne lesions developing post—inflammatory hyperpigmentation．SPF contained sunscreens are recommended for all skin types to use．【72】Nevertheless，sunscreens are regularly irritating the skin and many sunscreens with high SPF are heavy base，acnegenic and comedogenic．[73】Physical blockers acted sunscreens Can cause problems for oily and acne prone skin because they are made with heavy opaque occlusive bases．However，in our study，we found that there is negative relationship between acne severity and sunscreen，meaning that people without daily sunscreen use were more likely to develop SeVere aCne． Acne vulgaris is often associated、析t11 numerous psychological comorbidities with women more prone to emotional and behavioral difficulties than men．[84，91．93]Several of these studies mention not succeeding at school，low friendships，lack of romantic relationships and personal intimacy as predominant findings．Other studies have also discovered additional evidence of psychosocial impairment，showing associations between acne and attention deficit disorder，insomnia，poor body image，and body dysmorphic disorder．[92,94]In addition，several studies have also revealed association of acne with diminished self-esteem，anxiety，depression，social isolation and suicide．【92，93】 One study in China analyzed the psychological well being of those suffering from severe acne and found that their cumulative negative life events，in fact，accelerated both the occurrence and the exacerbation of acne．[951 In this study，we found that emotional impact is not associated with acne severity significantly with the fact that patients with more severe acne have higher emotional impact scores．Our study strictly evaluate the emotional impact of acne in study population，therefore the results neither 42 万方数据 圣皇堂!竺曼坐!!!望!堕翌型竺婴!!堡 里!!!堕!!竺呈 compatible to above．mentioned studies nor cover the overall patients’quality of life． Epidemiological studies of acne and its associating factors have been primarily conducted in the West。and 1imited studies have been performed in Asian，Chinese patients particularly．Herein，we present the findings of a study in our dermatology clinics．We believe that this study outcome will be useful in the future．Larger， community．based，epidemiological studies are necessary to better allocate the characteristics of acne patients in Asian，Chinese patients especially．In the future studies，other factors such as sun exposure，smoking，alcohol consumption，stress and constipation should also been taken into consideration． 43 万方数据 兰皇笪!竺曼旦里!!!!!!壁垒!型竺：!羔!!!! 堡旦呈!!旦!!旦里1 5．Conclusions We believe that this study provides innovative understanding of acne in the population and significantly magnifies the patient profile．There now seems to be good evidence that acne Can endure well into adulthood．When describing the two types of post．adolescent acne，the terminologies‘late onset’and‘persistent’"acne are now commonly recognized．Studies have found that genetic factors play a more critical part in adolescent acne and that post adolescent acne is more affected by acquired factors， such as environmental effects，lifestyle factors and hormone dysregulation． In conclusion，we found that： [1]Adolescent acne mainly affects and more severe in men while adult acne mainly affects women． [2]Premenstrual flare is associated with both adolescent and adult acne． [3]Adolescent acne and adult acne had similar presentations of facial acne． [4]Patients with positive family history had significantly higher risk of developing more severe acne． [5]Patients without daily sunscreen and moisturizer use had significantly higher risk of developing more severe acne． [6]There was no difference in acne severity among those who had or had not prior treatment． [7]Patients with more severe acne had greater emotional impact of acne． [8]Other confounding factors such as smoking，alcohol consumption，constipation， stress，insomnia，Sun exposure and cosmetics were not associated with acne severity． 万方数据 兰堕!塑璺坐!!!型堡坚竺塑旦型! 兰!翌!堡!旦墅 6．Limitations This study limitation includes absence of control group and total reliance on patient self-report for history，history of treatment，behaviors and lifestyle factors．Firstly，the possibility of underestimating the family history of acne with great reliance on questionnaire might be greater in men subjects because they have the tendency to less be aware of their family history．Second，the disease severity is believed to be more severe since participating subj ects were those who visit our clinic pursuing acne treatment．Gender difference in family history may have risen from here，in that women tend to be more worried about their family history of acne and their disease grade．Third， patients could be previously treated or to be consulting a dermatologist for their acne before；a study、Ⅳith these restrictions may rather produce altered outcomes．Fourth， detailed frequency was not included in the consumption of food，smoking and alcohol questionnaire section。While these factors might be the appropriate tool to determine their impact on acne severity．Fifth，Cardiff Acne Disability Index or the Dermatology Life Quality Index(DLQI)was not used to analyze the quality of life impact of acne． This study strictly evaluating the emotional impact of acne in study population， therefore the results may not cover the overall patients’quality of life．Sixth，study subj ects are patients visiting dermatologic clinics for acne in one hospital，SO that the result might not reflect the whole Chinese population． 45 万方数据 Zhejiang University Master Thesis References References [1]．Goldsmith LA，Katz SI，Glichrest BA，et a1．Fitzpatrick’S Dermatology in General Medicine，8th edn．Mc Graw—Hill，New York：20 1 2． [21．Clinical Knowledge Summaries(CKS 20 1 1)Acne Vulgaris．Management． www．cks．nhs．uk／acne_vulgaris(Last accessed：May 1 7 20 1 2．) [3】．Simpson NB，Cunliffe WJ．Disorders of sebaceous glands．In：Burns T，Breathnach S，Cox N，Griffiths C，editors．Rook’S Textbook of Dermatology，7m ed．，Oxford： Blackwell publishing；2004．P．43．1-43．75． [4]．Jowett S，Ryan T．Skin disease and handicap：an analysis of the impact of skin conditions．Soc Sci Med 1 985；20(4)：425—9． [5]．Koo J．The psychological impact of acne：patients’perceptions．J Am Acad Dermatol 1995；32(5 Pt 3)：$26-30． [61．Koo JY，Smith LL．Psychological aspects ofacne．Pediatr Dermatol 1991；8(3)：185— 8． [7]．Krowchuk DP，Stancin T，Keskinen R，et a1．The psychosocial effects of acne on adolescents．Pediatr Dermatol 1991；8(4)：332-8． [8]．Smithard A，Glazebrook C，Williams HC．Acne prevalence，knowledge about acne and psychological morbidity in mid·adolescence：a community-based study．Br J Dermatol 200 1；1 45(2)：274-9． [9】．Preneau S，Dreno B．Female acne-a different subtype of teenager acne?J Eur Acad Dermatol Venere01．2012；26(3)：277—282． [1 0]．Shaw JC，White LE．Persistent acne in adult women．Arch Dermat01．200 1；1 3 7(9)： 1252．1253． [1 1]．Witkowski JA，Parish LC．The assessment of acne：An evaluation of grading and lesion counting in the measurement of acne．Clin Dermatol 2004；22：394-7． [1 2]．Halder RM，Grimes PE，McLaurin CI，et a1．Incidence of common dermatoses in a predominantly black dermatologic practice．Cuffs．1 983；32(4)：388，390． [1 3]．Shah SK，Bhanusali DG，Sachdev A，et a1．A survey of skin conditions and concerns in South Asian Americans：a community-based study．J Drugs Dermatol， 46 万方数据 兰皇笪!竺墨旦呈!!!!!!堡坚竺!!!里篁堡 垦!垒!!里!竺 201 1：1U：524。528． [1 4]．Davis SA，Narahari S，Feldman SR，et a1．Top dermatologic conditions in patients of color：an analysis of nationally representative data．J Drugs Dermat01．20 1 2；1 1： 466．473． [1 5]．Alexis AF，Sergay AB，Taylor SC．Common dermatologic disorders in skin of color：a comparative practice survey．Cuffs．2007；80：387—394． [16]．Poll F．Acne on pigmented skin．Int J Dermat01．2007；46(Suppll)：39_41． [1 71．Child FJ，Fuller LC，Higgins EM，Du Vivier AWP．A study of the spectrum skin disease occuring in black population in south—east London．Br J Dermat01．1 999； 141：512．517． 【1 8]．Perkins AC，Cheng CE，Hillebrand GG，et a1．Comparison of the epidemiology of acne vulgaris among Caucasian，Asian，Continental Indian and African American women．J Eur Acad Dermatol Venere01．20 1 1；25：1 054—1 060． [1 9]．Callender VD．Acne in ethnic skin：special considerations for therapy．Dermatol Ther．2004；17：184—195． [201．Yin NC，McMichael AJ．Acne in patients with skin of color：practical management． Am J Clin Dermat01．2013 Nov 5．[Epubahead ofprint]． [2 1]．Davis EC，Callender VD．A review of acne in ethnic skin：pathogenesis，clinical manifestations and management strategies．J Clin Aesthetic Derrnat01．2 0 1 0；4：24— 28． 『22]．Shah SK，Alexis AF．Acne in skin of color：practical approaches to treatment．J Dermatol Treat．2010；21：206．21 1． [23]．Morrone A，Franco G，Valenzano M，et a1．Clinical features of acne vulgaris in 444 patients with ethnic skin．J Dermat01．201 1；38：405—408． [241．Innocenzi D．Acne aspetti clinico—patologici，terapeutici e cosmetologici． Viareggio，Italy：J Medical Books Edizioni，2008． [25]，Shen Y，Wang T，Zhou C，Wang X，et a1．Prevalence of acne vulgaris in Chinese adolescents and adults：a community—based study of 1 7，345 subjects in six cities． Acta Derm Venereol 2012；92：40-44． 【26]．Cunliffe WJ，Gould DJ．Prevalence of facial acne vulgaris in late adolescents and 万方数据 Zhejiang University Master Thesis References inadults．BMJ 1979；1：1109—1110． [27]．Goulden V，Stables GI，Cunliffe WJ．Prevalence of facial acne in adults．J Am Acad Dermatol 1 999；4 1：577-580． [28]．Schafer T，Niehaus A，Vieluf D，Berger J，Ring J．Epidemiology of acne in the general population：the risk of smoking．Br J Dermatol 200 1；1 45：1 00—1 04． [291．Stem RS．The prevalence of acne on the basis of phy’sical examination．J Am Acad Dermat01 1992；26：93 1．935． [30]．Collier CN，Harper JC，Cafardi JA，Cantrell WC，Wang W，Foster KW，et a1．The prevalence of acne in adults 20 years and older．J Am Acad Dermatol 2008；58：56． 59． [3 1】．Poli F，Dreno B，Verschoore M．An epidemiological study of acne in female adults： results of a survey conducted in France．J Eur Acad Dermatol Venereol 200 1；1 5： 541．545． [321．Dreno B，Layton A，Zouboulis CC et a1．Adult female acne：a new paradigm．J Eur Acad Dermatol Venereol CC 2013；27：1063—1070． [3 3 1．Faure M，Pawin H，Poli F，Revuz J，Beylot C，Chivot M，Auffret N，Moyse D， Dreno B．Factors influencing the clinical evaluation of acne。Acta Derm Venereol 2009；89：369-371． [34]．Evans DM，Kirk KM，Nyholt DR，Novae C，Martin NG．Teenage acne is influenced by genetic factors．Br J Dermat01．2005；1 52： 5 79．5 8 1． [35]．Xu SX，Wang HL，Fan X，Sun LD，Yang S，Wang PG，Xiao FL，et a1．The familial risk of acne vulgaris in Chinese Hans：a case controlled study．J Eur Acad Dermatol Venere01 2007；2 1(5)：602—605． [3 6]．Layton AM，Henderson CA，Cunliffe WJ．A clinical evaluation of acne scarring and its incidence．Clin Exp Dermatol 1994；19(4)：303—8． [3 7]．Yeung CK，Teo LH Y．Xiang LH．et a1．A community—based epidemiogical study of acne vulgaris in Hong Kong adolescents．Ada Derm Venereol 2002；82：1 04． [3 8]．Chan HHL．Manstein D，Yu CS．et a1．The prevalence and risk factors of post— inflammatory hyperpigmentation after fractional resurfacing in Asians．Lasers Surg Med 2007；39；381—5． [3 9]．Tanghetti EA，Kawata AK，Daniels SR，Yeomans K，Burk CT，Callender VD． 48 万方数据 Zhejiang University Master Thesis RefeFences Understanding the burden of acne of adult female acne．J Clin Aesthet Dermatol 2014；7：22-30． [40]．Williams M，Cunliffe WJ．Explanation for premenstrual acne．Lancet． 1 973；2： 1055．1057． [4 1]．Shaw JC．Low dose adjunctive spironolactone in the treatment of acne in women：a retrospective analysis of 85 consecutively treated patients．J Am Acad Dermatol 2000；43：498—502． 【421．Fisher DA．Desideratum dermatologicum—cause and control of premenstrual acne flare．Int J Dermatol 2000；39：334—336． [4 3 1．Tehrani R，Dharmallingam M．Management of premenstrual acne with Cox-2 inhibitors：a placebo controlled study．Indian J Dermatol Venereol Leprol 2004；70： 345．349． [441．Cho YJ，Lee DH，Hwang EJ，et a1．Analytic study of the patients registered at Seoul National University Hospital acne clinic．Korean J Dermatol 2006；44：798- 804． [45]．Kligman AM。Post—adolescent acne in women．Cuffs 1 991；48：75—77． [461．Lane L，Peck GL，Loriaux DL，et a1．Adrenal androgen secretion in post—adolescent acne．J Clin Endocrinol Metab 1991；73：380—384． [47]．Lucky AW，Rosenfield RL，McGuire J，et a1．Adrenal androgen hyper— responsiveness to adrenocorticotropin in women with acne and／or hirsutism．J Clin Endocrinol Metab 1 986；62：840—848． [48]．Schmidt JB，Lindmaier A，Spona J．Endocrine parameters in acne vulgaris． Endocrinol Exp 1 990；24：457—464． 【49]．Born J，Hansen K，Marshall L，et a1．Timing the end of nocturnal sleep．Nature 1999；397：29-30． [5 0]．Denda M，Takei K，Denda S．How does epidermal pathology interact with mental state?Med Hypotheses 2013；80：194—196． 【51]．Joo EY，Yoon CW，Koo DL，Kim D，Hong SB．Adverse effects of 24 hours of sleep deprivation on cognition and stress hormones．J Clin Neurol 20 1 0；8：1 46．1 50． [52]．Rombouts S，Nij sten T，Lambert J．Cigarette smoking and acne in adolescents： results from a cross—sectional study．J Eur Acad Dermatol Venereol 2007；2 1：32乳 49 万方数据 Zhejiang University Master Thesis References 333． [53]．Mills CM，Peters TJ，Finlay AY．Does smoking influence acne?Clin Exp Dermatol 1993；18：100—101． [54]．Higgins E，du Vivier A．Alcohol intake and other skin disorders．Clin Dermatol 1999；17：437_441． [55]．Parish LC，Fine E．Alcoholism and skin disease．hat J Dermatol 1985；24：300—1． [56]．Higgins EM，du Vivier AWP．Cutaneous disease and alcohol misuse．Br Med Bull 1 994；50：85—98． [5 7]．Klaz I，Kochba I，Shohat T，et a1．Severe acne vulgaris and tobacco smoking in young men．J Invest Dermatol 2006； 1 26：1 749—1 752． [5 8]．Zhang H，Liao WQ，Chao W，Chen QL，Zeng HX，et a1．Risk factors for sebaceous gland diseases and their relationship to gastrointestinal dysfunction in Han adolescents．Journal ofDermatol 2008；35：555-561． [59]．Walravens PA．Zinc metabolism and its implications in clinical medicine．West J Med 1979；130：133—142． [60]．Dessinioti C，Katsambas AD．The role of Propionibacterium acnes in acne pathogenesis：facts and controversies．Clin Dermatol 20 1 0；28：2-7． [6 1]．Suh DH，Kwon HH．What’S new in the physiopathology of acne?Br J Dermatol 2015；172(Suppl 1、：13-9． [62]．E1 Darouti MA，Zeid OA，Abdel Halim DM，Hegazy RA，Kadry D，Shebab DI， Abdelhaliem HS，Saleh MA．Salty and spicy food；are they involved in the pathogenesis of acne vulgaris?A case controlled study．J Cosmet Dermatol 20 1 5． [Epub ahead print]． [63]．Green J，Sinclair RD．Perception of acne vulgaris in final year medical student written examination answers．Austral J Dermatol 2001；42：98-101． [64]．Fulton JE Jr，Plewig G，Kligman AM．Effect of chocolate on acne vulgaris．JAMA 1969；210：2071-2074． [65]．Smith RN，Mann NJ，Braue A，et a1．A low glycemic load diet improves symptoms in acne vulgaris patients：a randomized controlled trial．Am J Clin Nutr 2007；86： 107．115． [66]．Adebamowo CA，Spiegelman D，Danby FW，et a1．High school dietary dairy intake 50 万方数据 Zhejiang University Master Thesis References and teenage acne．J Am Acad Dermat01 2005；52：207-2 1 4． [67]．Adebamowo CA，Spiegelman D，Berkey CS，et a1．Milk consumption and acne in adolescent gifts．Dermatol Online J 2006；1 2：1． [68]．Adebamowo CA，Spiegelman D，Berkey CS，et a1．Milk consumption and acne in teenaged boys．J Am Acad Dermatol 2008；58：787-793． [693．Dreno B，Thiboutot D，Layton M，Berson D，Perez M，Kang S．Large scale intemational study enhances understanding of an emerging acne populaion：adult females．J Eur Acad Dermatol Venereol 2015；29(6)：1096—1 106． [70]．Williams HC，Dellavalle RP，Garner S．Acne vulgaris．Lancet．15．2012；379：361- 379． [7 1]．Lynde C．Moisturizers for the treatment of inflammatory skin conditions．J Drags Dermat01．2008；7：1038—1043． [721．British Association of Dermatologists．Sunscreen and skin cancer factsheet． Available from URL：http：／／www．bad．org．uk／public／cancer／ BAD一&LBSF—SUNSCREEN_FACT SHEET．pdf[Accessed 2008 Jun 1 1] [73]．Funk JO，Dromgoole SH，Maibach HI．Sunscreen intolerance．Contact sensitization，photocontact sensitization，and irritancy of sunscreen agents． Dermatol Clin 1995；13(2)：473-81． [74]．Bataille V，Snieder H，MacGregor AJ et a1．The influence of genetics and environmental factors in the pathogenesis of acne：a twin study of acne in women．J Invest Dermat01 2002；1 19：13 17_1322． [75]．尉rk KM，Evans DM，Farthing B et a1．Genetic and environmental influences on acne in adolescent twins．Twin Res 200 1；4：1 90． [76]．Zhang H，Liao W，Chao W，Chen Q，Zeng H，Wu C，Wu S，Ho HI．Risk factors or sebaceous gland diseases and their relationship to gastrointestinal dysfunction in Han adolescents． [77]．Ashbee HR，Evans V．Immunology of disease associated with Malassezia species． Clinical Microbiol Rev 2002；15：21—57． [78]。Webster GF．Ache vulgaris．BMJ 2002；325：475-479． [79]．Adityall B，Kumari R，Thappa DM．Scoring systems in acne vulgaris．Indian J Dematol Venereol Leprol 2009；75(3)：323—326． 51 万方数据 Zhejiang University Master Thesis References [80]．Seattle WI．GBD Compare．Seattle：University of Washington；20 1 3． [81]．Wolkenstein P，Grob JJ，Bastuji-Garin S，Ruszczynski S，Roujeau JC，Revuz J． French people and skin diseases：results of a survey using a representative sample． Arch Dermat01．2003；139(12)：1614—1619． [82]．Rea JN，Newhouse ML，Halil T．Skin disease in Lambeth．A community study of prevalence and use ofmedical care．Br J Prev Soc Med．1976；30(2)：107-114． [83]．Johnson MT，Roberts J．Skin conditions and related need for medical care among persons 1—74 years．United States，1971-1974．Vital Health Stat．1978；1 1(212)：i-v， 1．72． [84]．Bhate K，William HC．Epidemiology of acne vulgaris．Br J Dermat01．2013；168(3)： 474．485． [85]．Melnik BC，Zouboulis CC．Potential role of FoxO 1 and mTORC 1 in the pathogenesis ofWestern diet—induced acne．Exp Dermat01．2013；32(5)：31 1-315． [86]．Melnik B．Dietary intervention in acne：Attenuation of increased mTORCl signaling promoted by Westem diet．Dermatoendocrin01．2012；4(1)：20—32． [87]．Smith RN，Mann NJ，Braue A，Makelainen H，Varigos GA．The effect of high protein，low glycemic load diet versus a conventional，high glycemic load diet on biochemical parameters associated with acne vulgaris；investigator—masked， controlled trial．J Am Acad Dermat01．2007；57(2)：247—256． [88]．Koldovsky 0．Hormones in milk．Life Sci．1980；26(22)：1833—1836． [89]．Yeung A，Sheehan J．Hormone Concentrations in Milk and Milk Products[Letter from FDA Center for Food Safety and Applied Nutrition]．Washingon，DC：US Food and Drug Administration；20 1 2． [90]．Danby FW．Acne Causes and Practical Management．Hoboken，NJ： Wiley Blackwell；2015． [91]．Halvorsen JA，Stem RS，Dalgard F，Thoresen M，Bjertness E，Lien L．Suicidal ideation，mental health problems，and social impairment are increased in adolescents with acne： a population-based study． J Invest Dermat01． 201 1；131(2)：363—370． [92]．Silverberg JI，Silverberg NB．Epidemiology and extracutaneous comorbidities of severe acne in adolescence：a US population—based study．Br J Dermat01． 52 万方数据 Zhejiang University Master Thesis References 2014；170(5)：1 136--1 142． [931．Smithard A，Glazebrook C，Williams HC．Acne prevalence，knowledge about acne and psychological morbidity in mid-adolescence：a community-based study．Br J Dermat01．200 1；1 45(2)：270279． [94]．Spencer EH，Ferdowsian HR，Barnard ND．Diet and acne：a review ofthe evidence． Int J Dermatil．2009；48(4)：339-347． [95]．Wen L，Jiang G，Zhang X，Lai R，Wen X．Relationship between acne and psychological burden evaluated by ASLEC and HADS surveys in high school and college students from central China．Cell Biochem Biophys．2015；71(2)：1083— 1088． [96]．Jugeau S，Tenaud I，Knol AC，et a1．Induction of toll—like receptors by Propionibacterium acnes．Br J Dermat01．2005；153(6)：1105—1113． [97]．Kim J．Review ofthe innate immune response in acne vulgaris：activation of Toll— like receptor 2 in acne triggers inflammatory cytokine responses．Dermatology． 2005；21 1(3)：193-198． 万方数据 墨垫笪!塑曼旦呈!!!望!堡垒!型!!里!里! 兰垫!!塑墨!!!!!!! Literature Review PoSTINFLAMMAToRY HYPERPIGMENTATIoN A review of evolving therapy for PIH Clarissa Dwipuspa Wijaya Literature review Zhu Kejian Disorder of hyperpigmentation is the outcome of an increase in melanin production and a change in activated melaIlocNes density in skin．It Can be circumscribed，diffuse， reticulated or linear，and such pattems can aid in a specific diagnosis．Melasma and postinflammatory hyperpigmentation(PIH)are two predominant disorders of hyperpigmentation． Melasma，also called chloasma is an acquired hyperpigmentation—affecting dwoman primarily．It is a circumscribed hypermelanosis with distinctive irregular brown patches on sun-exposed skin，most frequently involving the forehead，the nose， the upper lip，the chin and malar prominences．【1，2】Sheth and Pandya【2】stated that the centrofacial pattern as the most frequent pattern，characterized by lesions on the cheeks， forehead，nose，upper lip，or chin．The malar pattern comprises of lesions primarily on nose and cheeks．The mandibular pattern comprises of lesions on the mandible and ramus．Though its precise pathogenesis is unidentified，multifactorial etiology such as racial predilection and genetics，exogenous hormonal therapy，pregnancy，ultraviolet therapy exposure or irradiation，cosmetics，may be linked to melisma exacerbation and pathogenesis．[341 Postinflammatory hyperpigmentation(PIH)is the skin’S reactive hypermelanosis． It shows as asymptomatic lesions such as macules or patches that depend on the contributing pathology might be divergent in size and distribution．It involves areas of previous cutaneous inflammation，such as eczema，drug reactions，acne，trauma such as bums and friction，chemical peelings and laser applications．There is either overload production of melanin or an abnormal distribution of melanin pigment deposited in the eDidemlis and／or demis in PIH．[61 54 万方数据 兰皇笪!塑曼旦呈!∑!!!!堕坚塑竺里竺堡 生韭!望!坚坐!!!!!! These disorders are usual and upsetting，especially in higher Fitzpatrick skin types (skin of color)patients．It is regularly stirring to treat and have been confirmed to lead to a negative impact on quality of life．o¨Due to limitations in its efficacy，safety and cost considerations of accessible therapies，a single treatment modality for hyperpigmentation is nOW missing．Efficacious treatment naturally involves a conj unction between topical agents with or without in—clinic procedures，using different mechanisms of action of every agent or treatment modality as well as patience and time． The treatment for both melasma and PIH could carry a challenge for both of the phrrsicians and patients．This review will discuss the available approach therapy for postinflammatory hyperpigmentation correspondingly． 1．MEDICAL’I’HERAPY Initial management of PIH should address the underlying inflammation etiology，if the inflammation still active；this will stop any further pigmentary alteration．Yet，the initiated treatment itself might have the prospective to cause irritation resulting in Pm exacerbation．【7】The patient’S assessment of the treatment should always be included at each stage of treatment． 1．1 PHoToPRoTECTIoN Photoprotection should be initiated early and during the treatment process．It is an essential factor of Pill treatment and is directed to prevent the disorder from getting worse．[71 Broad．spectrum sunscreens use and sun avoidance are crucial，particularly in darker skin color individuals who might not be aware of the darkening effects UV radiation has on hyperpigmentation．[1,71 Since they are at bigger risk of vitamin D insufficiency，adjunctive treatment with day-to—day dose of 1 000 IU vitamin D is recom瑚ended．[7，8] 1．2HYDROQUINONE The use of the phenolic compound hydroquinone remains one of the mainstays in treating PIH．This skin lightening medication acts by blocking the 55 万方数据 Zhejiang University Master Thesis Literaturte review dihydroxyphenylalanine(DOPA)conversion to melanin through obstructing the enzyme tyrosinase，the fundamental step in synthesis of melanin．[91 It call also work through inhibiting synthesis of RNA，melanosome degradation by auto—oxidation and phenol oxidases，and selective cytotoxicity toward melanocytes．It is available at a 2％up to 1 0％concentration．The lower 2％concentration may be effective for milder forms of pigment accumulation and deposition．For more severe clinical phenotypes，higher 1 0％ concentration is used generally．Enduring topical hydroquinone use，even at smallest concentration，or higher，tend to induce exogenous ochronosis and irritation，remarkably with the darker phototypes．【10]While as a monotherapy，hydroquinone’S effectiveness is approximately seen after 20 weeks of treatment and efficacy plateaus after 6 months． Efficient outcome will be produced when applied twice daily and entire facial area application is a must since localized or so-called spot treatment can result in“bull’S 11 eye”discoloration areas．[1 Topical hydroquinone is combined with a topical retinoid． such as 0．1％tretinoin，antioxidants，glycolic acid，steroids，or sunscreen to increase its efficacy for more severe lesion．Yet，none of these treatments produced a validated outcome measure to determine improvement mainly in PIH．TriLuma(Galaderma，Fort Worth，TX，USA)is a less irritating formulation，which has 0．05％tretinoin，4％ hydroquinone，and O．0 1％fluocinolone acetonide．It has been used to treat both PIH and melasma with promising results．However，because of steroid，steroid-related side effects such as steroid ache and telangiectasia have been detected after 8 weeks of therapy， 1．3 MEQUINOL Mequinol is an altemative and derivative form of 4-hydroxyanisole，which found to be less irritating than hydroquinone．[13】It is accessible in a concentration of 2％and is formulated with 0．01％tretinoin，penetration enhancer and a retinoid acid normally． 【14】Mequinol could effectively treats solar lentigines in all patients[13-151 including ethnic populations have been revealed in some large clinical studies[16】；but merely small clinical studies have evaluated its efficacy in treating PIH．[17-19】One comparative 56 万方数据 Zhejiang University Master Thesis Literaturte review study[17】discovered alike effectiveness of topical mequinol 2％一tretinoin 0．01％to 4％ HQ in mild to moderate PIH among skin of color patients． 1．4 NONPHENOLIC COMPoUNDS Retinoids are functional and structural vitamin A analogues that have been widely used in the populmion．It is successful when being used alone or in conjunction witll other agents in treating PIH．Many biological properties utilized by retinoids to lighten the skin．Topical tretinoin，is a first genermion，naturally occurring metabolite of retinoid．[201 Ranging from 0．01 to 0．1％，tretinoin Can be formulated in crealns，gels and microsphere gels that lead to less irritation caused by the controlled release of tretinoin． [21,22]In a clinical trial with black patients conducted by Callender and colleagues[23】， 0．1％tretinoin was significantly more effective in treating PIH than the control；though half of the patients established retinoid dermatitis，which is the concern in skin of color when using retinoids．To prevent retinoid dermatitis，dosage titration，alternate—day use and dilution of the tretinoin with a moisturizer base could be done．The newer，retinoids third generation，tazarotene and adapalene，are topical synthetic agents that are efficient in treating PIH as well．Both agents have been found to effectively and safely treat PIH in clillical studies，mainlV PIH induced by acne and in individuals with darker skin．[24,251 A first generation，isotretinoin，is naturally occurring retinoid that is accessible in both topical and oral formula．In treating severe acne，oral isotretinoin is very successful． Nevertheless，there also has been a case reported of significant PIH resolution in an Asian Datient after oral isotretinoin therapy．【26】 Azelaie Acid is a dicarboxylic acid that appears naturally and is isolated from the pathogenic yeast of pityriasis versicolor；Malassezia furfur，and has been demonstrated to be successful in treating PIH．【27]Available formulations include a gel with 1 5％ concentration that normally used to treat rosacea，or a cream with 20％concentration that is normally used to treat melasma and acne in accumulation to PIH．A study by Lowe et al[281 was piloted to determine the effectiveness of azelaic acid in IV to VI skin types patients with PIH or melasm．They demonstrated that AA for those skin types was both effective and safe with mild and transient side effects，which also supported by 57 万方数据 Zhejiang University Master Thesis Literaturte review several other studies[29-3 1】；however，to determine its effectiveness for other skin types， larger studies are required． Ko j ic Acid is a Acetobacter，Aspergillus，and Penicillium fungal metabolite．Koj ic acid acts as tyrosinase inhibition and is accessible from concentrations of 1％to 4％．To improve efficacy，it can be prepared谢th other skin—lightening medications such as hydroquinone and glycolic acid as well．Several studies comprising Asian and Caucasian patients have revealed melisma improvement with conjunction therapy of hydroquinone and KA 2％．[32,331 Hence，those patients not seeing results from hydroquinone may benefit by adding kojic acid to their treatment regime．However， studies evaluating its efficacy in treating PIH are needed．In OTC cosmeceutical formulations，kojic acid often becomes a general adjunctive ingredient leading to increased offender for allergic contact dermatitis；therefore，its sensitizing potential should not be ignored． Arbutin is the bearberry pear or shrub dried leaves，or blueberry plants extraction， and HQ’S other derivative with no melanotoxic effects．[14,34]Its efficacy is dose dependent，but a paradoxical hyperpigmentation Can be caused with higher concentration．[351 Deoxyarbutin and alpha-arbutin are artificial forms of arbutin with ability to inhibit tyrosinase greater．[36,37]One study showed that arbutin was effective in treating solar lentigines in lighter phototypes but failed to have an effect in darker- skinned patients．【371 Nonetheless，lack clinical studies have evaluated arbutin in treating PIH among patients with darker skin phototypes． Niacinamide or niacin，is the physiologically active byproduct of vitamin B3，and has been revealed to decrease melanosome transfer to keratinocytes from melanocytes without obstructing enzyme tyrosinase or proliferation of cell．It might inhibit cell— signaling pathways as well．【38]It is a stable array of compounds and is not inactivated by moisture，light，acids，oxidizers，or alkalis．【39】From 2％to 5％，topical niacinamide alone or together with N—acetyl glucosamine has revealed particular effectiveness in treating fair skinned patients and Asians‘melasma and UV induced hyperpigmentation [38,40,41】；but its efficacy has not been shown in darker phototypes． N-acetyl glucosamine(NAG)found throughout human tissues and nature，all amino sugar that is originated from hyaluronic acid．[42]It has been described to decrease 5R 万方数据 Zhejiang University Master Thesis Literaturte review melanogenesis；however，due to its instability，topical agent formulation has not been easy．Lately，attention has now stirred to NAG—contained cosmeceuticals development because of its better stability，upright skin pene订ation，and overall tolerability．NAG is used usually as monotherapy in concentrations of 2％or as addition therapy with niacinamide，which due to two different mechanisms of depigmentation at work might yield a better effect．[42】Many controlled，double blinded trials have proven NAG alone or NAG+niacinamide combination therapy to effectively and safely reduce hyperpigmentation resulting from solar radiation in Japanese and Caucasian patients． [41,421 Modest irritation of the skin described in small quantity of patients using NAG． Yet，larger studies are necessary to be able to define NAG role in treating all skin types patients with PIH． Asorbie acid，or vitamin C，is an antioxidant attained from certain fruits and vegetables．【39】Several studies have demonstrated that AA has anti—inflammatory and 【43-48】 photoprotective properties despite skin lightening and antioxidant effects． Esterified byproducts such as magnesium ascorbyl phosphate and ascorbyl--6-‘palmitate were produced because of the unstable formulations of early AA．【43】Its safety and efficacy were reported in Asian and Latino patients；nonetheless，utmost studies presented did not include PIH treatment，but only melasma．[49,501 Licorice root extract，a仔equent found component in several skin—lightening cosmetics[141 is used in treating an extensive diseases variation even outside the field of dermatology because of its anti-inflammation， antimicrobial， antiviral， and anti— carcinogenic properties．[511 Limited clinical studies have evaluated its efficacy in treating dermatological diseaseas．20 Egyptian women in a study revealed that the use of topical liquiritin cream(1 g／day)for four weeks was both effective and safe in treating melasma with mild irritation seen in one fifth of the patients．[521 Advance studies with ethnic patients are necessary to calculate its efficacy and safety in treating PIH． Soy proteins are another naturally occurring compounds that regarding to their medicinal purposes has gained much attention．Soy proteins such as Bowman Birk Inhibitor(BBI)and soybean trypsin inhibitor(STI)obstruct the activation of protease— activated receptor 2 cell receptors，leading to reversible depigmentation as a consequence of reduced melanosomes phagocytosis into keratinocytes．【53】Soy is 万方数据 圣垒笪!塑曼旦呈!!!!!!堡坚堡!!堡!!垫 生堡竺!堡垒!!!兰!! curlrently being produced alone or combined with other agents such as sunscreen and retinol into cosmetics，especially moisturizer，not only to aid photodamage signs reduction but also hyperpigmentation in all skin types．[54-56]One clinical study of post acne hyperpigmentation in Fitzpatrick skin types III and IV among Hispanic，African American，and Asian patients was piloted to defme OTC treatment of acne comprising retinol，salicylic acid，and total soy safety and efficacy．[571 With the use of soy formulation，compared to placebo，there was a significant improvement of PIH． Products that contain soy are commonly well tolerated。[141 Yet，larger scale clinical trials are required． 2．S URGlCAL’l’HERAP Y The use of chemical peeling is the next promising step in treating hyperpigmentation．There is a comprehensive variation of chemical peels in an array of strengths，and care，which should be taken into consideration．Choosing and using the precise peel Can prevent irritation that Can further avoid aggravate PIH and other complication such as new depigmentation areas，hypertrophic scarring，and formation of keloid．[581 Thus，among darker phototypes IV to VI，chemical peeling should be measured with caution，and anticipation of new hyperpigmentation by越tiating skin— lightening therapy before hyperpigmentation develops．A thorough history，including cu玎ent topical and oral medications，other dermatological diagnosis，former reactions to different cosmetic procedures，herpes simplex virus(HSV)infection history and a careful skin investigation should be taken before the procedure．[59-61]Patients should be well informed on the prominence of photo-protection to prevent PIH worsening resulting from chemical peeling．The mechanism involves the melanin removal rather than inhibiting melanocytes or melanogenesis process by previous treatments．The complication chances from chemical peeling rises with the insult depth created，thus， superficial peels reveal the smallest risk of complications though subsequent hyperpigmentation call still be seen．Patients with oily skin and acne prone skin are favored using SA peels and began at a lowest strength 4 weeks after topical therapy is initiated．On the other hand，glycolic acid is suitable for dry skin patients． 60 万方数据 圣皇笪!婴曼旦呈!!!望堕丝竺!笪堡!!!! 兰!堕塑坐!!兰!1 2．1 GLYCOLIC ACID PEELS(GA) GA is obtained in sugarcane，alphaohydroxy acid(AHA)naturally occurred，which stimulates epidermolysis，increases synthesis of dermal collagen，and diffuses melanin of basal layer．[60-62]Ranging from 20．70％in concentration，and a common element in skin lightening creams with 1 0％concentration，in which terminating the peel involves neutralization wim sodium bicarbonate and water．Multiple studies have been accomplished to show the GA peels safety and efficacy in melasma and PIH．Such peels have also been shown to be use safely in skin type IV to VI．Burn and colleagues[63J proved that adding GA peels to topical treatment in skin types IV to VI patients resulting in a more rapid and greater improvement compared with controls and topical treatment a】one． 2．2 SALICYLIC ACID PEELS(SA) A beta．hydroxy acid that is willow tree bark derivation，and by interrupting the linkages of intercellular lipid between epithelioid cells．provokes keratolysis．[9，60】The available concentrations are ranging from 20 to 3 0％．It is considered as self- neutralizing peels that Can be seen as an ice frost once the peel neutralizes．SA peels with 3 0％were undergone for three months every two weeks in study of 24 acne— induced PIH Korean patients．Calorimetric analysis indicated a significant improved PIH lightness from baseline to the first post-peel period；however，no significant final lightening levels．Nonetheless，erythema was decreased significantly，while dryness， scaliness．and greasiness were improved during clinical examination．[删SA peels have also been demonstrated to be safe and effective for patients with higher skin photoypes V and VI．【65】 2．3 TRICHLORACETIC ACID PEELS(TCM Chemical peels superficially could be achieved using trichloracetic acid or Jessner’S solution，start out at low concentrations and be slowly increased continually while monitoring side effects such as erythema，burning，PIH，and recurrence of herpes simplex，desquamation and vesiculation superficially．Both of these chemical peels have 61 万方数据 Zhejiang University Master Thesis Literaturte review been effective in treating melasma．[66-67]Nevertheless，clinical evidence proving its use to treat PIH patients is lacking． 3．CoSMlE’I’lC CUVER-Ur Suitable in concealing pigmented scars，vascular lesions and conditions of persistent skin conditions that are not responsive to both of medical and surgical therapies．【68】These methods carl benefit patients by covering and relieving misery concerning their appearance physically while also significantly improves life quality．[69- 701 It is useful when the disease effected highly visible boay parts，including the face， neck and hands and particularly in darker skinned patients where more obvious pigmentary alteration may be found．[711 Good cosmetic cover incorporates a natural appearance and ungreased feeling，while should provide long lasting and waterproof coverage．It should be non-comedogenic and non-acnegenic while simple to apply．[72J Either subtle coverage or full concealment，[731 color correctors neutralize lesion intensity by using color opposite to lesion’S color．【68】 4．LASERS AND LIGH’11 BASED THERAP Y Laser and light therapy Can be a useful addition to therapy or altemative for treatment failure though the mainstay treatment of PIH is topical skin-lightening agents． Nevertheless，limited literatures have precisely evaluating treatment of PIH in all skin types with the use of these devices．Near infrared(755nm，1 064nm)，red(694nm)and Green(5 1 0nm，532nm)are pigment—specific laser that produce light to aim intracellular melanosomes specifically．[741 Nevertheless，due to variation of melanin absorption， complications including blistering，dyschromias，and SCarS call be produced if deeper targets are proj ected for laser energy．【75J The use of cooling devices and longer pulse durations Can deliver more safety whereas its efficacy in darker skinned patients still maintained．【75J The prosperous treatment of PIH with blue light photodynamic therapy， neodymium—doped yttrium aluminum garnet(Nd：YAG)laser，and fractional photothermolysis in higher skin phototypes have been shown in several case reports．[76- 781 62 万方数据 Zhejiang University Master Thesis Literaturte review 4．1 INTENSE PULSED LIGHT(IPL) This system has been used to handle hyperpigmentation and melasma in varied skin types，and has been used particularly in skin types IV and V．Wang and colleagues 【79】acknowledged improvement in patients skin types III and IV with refractory melasma，which were treated with 4 sessions of IPL and hydroquinone．They identified that the longer wavelengths(>600nm)should be used because of decreased competition from oxyhemoglobin with less vascular damage．However，exacerbation of subclinical melasma has been reported when aggressive fiuences of IPL are used．IPL induced erythema should lasts only for a few minutes，not hours．The longer the erythema lasts，the greater the risk of melasma-like post-treatment hyperpigmentation arises．However，larger studies assessing the function of this procedure in treating PIH are still required． 4．2NONABLATIVE LASERS Nonablative lasers are beneficial in treating PIH and melasma，especially in darker skin phototypes patients．The nonablative 1—64-nin Nd：YAG laser is frequently used to treat of these disorders．The longer pulse duration and wavelength are capable to target deeper into the dermis，targeting dermal melanin，which is often a component of both PIH and melasma．This laser also protects the epidermis from incidental damage that Can exacerbate both disorders．Q—switched laser is frequently used in darker skin patients．It has the facility to produce very short pulses with higher energy compared to continuous wave modellasers．It has pulse durations in the 10一to 100一nanosecond range as well as fluences in the 2一to 1 0一J／cm3 range．Q—switched ruby laser is suitable for phototypes IV or less because it radiates at 694nm and，Q—switches alexandrite is suitable for phototypes V or less because it radiates at 755nm，and Q-switched Nd： YAG laser and because it radiates at 1 064nm，is suitable for all skin types．Many confirmations established that these systems succeeded in treating melasma，while there was insufficient clinical evidence of its efficacy in treating PIH，such as a case report of the successful PIH treatment using Q—switched Nd：YAG laser by Cho and colleagues， 63 万方数据 [78】therefore more studies are needed to further assess its efficacy and safety in treating PIH． 4．3 FRACTIoNAL PHoToTHERMOLYSIS Alternative non．ablative laser procedure that engages a range of small laser beams to create microscopic treatment zones，several areas of microscopic thermal necrosis within the skin．Though this procedure destroys the epidermis and dermis within the microscopic treatment zones entirely，there only are few side effects and the 3- dimensional damage pattern quickly heals．It has been regularly used to treat photo— damaged skin，acne SCarS，fine wrinkles，and melasma．A case report suggested that fractional photo．thermolysis might be efficient to treat PIH[80】；however，larger clinical studies are necessary to further assess the role and efficacy of this procedure in treating PTH 4．4 ABLATIVE Sl(IN RESURFACING This procedure stimulates contraction and remodeling the post—treatment dermis via coagulation process，thus old epidermis is removed．Collagen denatures and shrinks by the heat produced under ablative resurfacing，causing a visible tightening of the skin． A controlled partial．thickness bum of the epidermis and partly of the dermis was yielded；therefore its use in phototypes V and VI is not suggested to avoid the risk of hyperpigmentation，delayed—onset hyperpigrnentation，and scarring．Interaction between tissue and laser light in the ablative regime is controlled by absorption of water；thus， the water absorption is a main factor in selection of wavelength．The 2940一m Er：YAG laser releases a wavelength of 2940 nlTl that is adj acent to the peak of water absorption and yields an absorption coefficient 1 6 times that of the C02 laser．The 2790-nnl Er： YSGG has a slightly shorter wavelength and assumed to ablate the top 1 0 to 30 nln of the epidermis，and below that the epidermis is coagulated．The perception of fractional therapy has also been related to the ablative wavelength lasers，and fractional ablation is becoming a progressively used modality for skin resurfacing．Fractional ablative C02 1asers have been revealed to lead to wound healing faster and reduce down time．[811 万方数据 Zhejiang University Master Thesis Literaturte review ●____-_--——————'_________-———______-—J————●__________-———________————--'_____———————''____—————_●_____●——________--—，—_—●____-_————————————————— SUMMARY This review provides an outline of the available treatment of hyperpigmentation， particularly PIH，which uses medical，surgical，and laser technologies．It is essential to start treatment early whereas taking caution to stop worsening of the pre—existing hyperpigmentation with the use of these agents is also needed．Chemical peeling and laser therapy are normally used in addition to topical regime；but，less aggressive modalities should be engaged when treating patients with phototype IV and greater． Patient should be educated about sun protection measures and sunscreen addition to the treatment routine will also be useful in treating patient with PIH．The use of validated outcome measures in clinical studies investigating the efficacy of therapies available for PIH would further support in the development of a standardized management for this difficult to manage condition．Further study is needed to define an ideal treatment regimen for PIH，because many of the previously investigated treatment modalities have potential to exacerbate and worsen inflammation． 65 万方数据 Zhejiang University Master Thesis Literaturte review References [1]．Stratigos AJ，Katsambas AD．Optimal management of recalcitrant disorders of hyperpigmentation in dark—skinned patients．Am J Clin Dermatol 2004；5(3)：1 61—8． [2]．Sheth VM．Pandya AG．Melasma：a comprehensive update：part I．J Am Acad Dermatol 20 1 1；65(4)：689-97． [3]．Pathak MA，Fitzpatrick TB，Kraus EW．Usefulness of retinoic acid in the treatment of melasma．J Am Acad Dermatol 1 986；1 5：894—899． [4]．Perez M，Sanchez儿，Aquils F．Endocfino-logic profile of patients丽th idiopathic melasma．J Invest Dermatol 1983；81：543—545． [5]．Pathak MA，Riley FC，Fitzpatrick TB．Melanogenesis is skin following exposure to long wave ultraviolet and visible light．J Investig Dermatol 1 962；39：435—443． [6]．Callender VD，St Surin-Lord S，Davis EC，Maclin M．Postinflammatory hyperpigmentation：etiologic and therapeutic considerations．Am J Clin Dermat01． 201 1；12：87—99． [7]．Davis EC，Callender VD．Postinflammatory hyperpigmentation：a review of epidemiology,clinical features，and treatment options in skin of color．J Clin Aesthet Dermatol 2010：3(7)；20—31． [8]．Academy Issues updated position statement on vitamin D．Available at： http：／／www．aad．org／stories-and-news／news-releases／academy-issues-updated- position-statement-on-vitamin-d．Accessed September 27，20 1 3． [9]．Grimes PE．Management of hyperpigmentation in darker racial ethnic groups． Semin Cutan Med Surg 2009；28：77—85． [10]．Burke P．Exogenous ochronosis：an overview．J Dermatol Treat 1997；8：21—6． [1 1]．Draelos Z．Hydroquinone：optimizing therapeutic outcomes in the clinical setting of melanin—related hyperpigmentation．Today’S Therapeutic Trends 200 1；1 9：1 9 1— 203． [1 2]．Taylor SC，Torok H，Jones T，et a1．Efficacy and safety of new triple—combination agent for the treatment of facial melasma．Cutis 2003；72：67—72． 66 万方数据 Zhejiang University Master Thesis Literaturte review [131．Fleischer AB，Schwartzel EH，Colby S1，et a1．The combination of 2％4- hydroxyanisole(Mequin01)and 0．0 1％tretinoin is effective in improving the appearance of solar lentigines and related hyperpigmented lesions in two double blind multicenter clinical studies．J Am Acad Dermatol 2000；42：459-467． [141．Draelos ZD．Skin lightening preparations and the hydroquinone controversy． Dermatol Ther 2007；20：308—3 13． [1 5]．Jarratt M．Mequinol 2％／tretinoin 0．0 1％solution：an effective and safe altemative to hydroquinone 3％in the treatment of solar lentigines．Cutis 2004；74：3 1 9—322． [161．Draelos ZD．The combination of 2％4-hydroxyanisole(mequin01)and 0．01％ tretinoin effectively improves the appearance of solar lentigines in ethnic groups．J Cosmet Dermatol 2006；5：239—244． [171．Taylor SC，Callender VD．A mulficenter，12 week，phase 3b trial：a combination solution of mequinol 2％／tretinoin 0．0 1％Vs．hydroquinone 4％cream in the treatment of mild to moderate postinflammatory hyperpigmentation[abstract]．J Am Acad Dermatol 2006；54(Suppl)：AB 1 94． [181．Callender VD．A small open—label study of a 2％4-hydroxyanisole solution of mequinol 2％／tretinoin O．0 1％VS hydroquinone 4％cream in the treatment of mild to moderate postinflammatory hyperpigmentation[Poster]．J Am Acad Dermatol 2004；50(Suppl)：A B 1 94． [191．Piacquadio D，Farris P，Downie J，et a1．Mequinol 2％／tretinoin 0．01％solution monotherapy and combination treatment of solar lentigines and postinflammatory hyperpigmentation[Poster]．J Am Acad Dermatol 2004；50(Suppl)：P145． [201．Kuenzli S，Saurat JH．Retinoids．In：Bolognia儿，Jorizzo儿，Rapini RP，eds． Dermatology．2加ed．Elsevier Mosby；2009． [211．Halder RM，Brooks HL，Callender VD．Acne in ethnic skin．Dermatol Clin 2003； 21：609—615． [22]．Embil K，Nacht S．The Microsponge Delivery System(MDS)：a topical delivery system with reduced irritancy incorporating multiple triggering mechanisms for the release ofactives．J Microencapsul 1996；13：575—588． [23]．Callender VD．Acne in ethnic skin：special considerations for therapy．Dermatol Ther 2004；17：184—195． 67 万方数据 Zhejiang University Master Thesis Literaturte review [24]．Jacyk AK，Mpofu P．Adapalene gel 0．1％for topical treatment of acne vulgaris in African patients．Cutis 200 1；68：48—54． [25]．Grimes P，Callender V．Tazarotene cream for postinflammatory hyperpigmentation and acne vulgaris in darker skin：a double—blind，randomized，vehicle—controlled study．Cutis．2006；77：45—50． [26]．Winhoven SM，Ahmed I，Owen CM，et a1．Postinflammatory hyperpigrnentation in an Asian patient：a dramatic response to oral isotretinoin(13一cis-retinoic acid)．Br J Dermat01 2005；152：368—369． [27]．Grimes PE．Management of hyperpigmentation in darker racial ethnic groups． Semin Cutan Med Surg 2009；28：77-85． [28]．Lowe NJ，Rizk D，Grimes P，et a1．Azelaic Acid 20％cream in the treatment of facial hyperpigmentation in darker-skinned patients．Clin Ther 1 998；20：945—959． [29]．Balina LM，Graupe K．The treatment of melasma：20％azelaic acid versus 4％ hydroquinone cream．Int J Dermatol 1991；30：893—895． [30]．Sarkar R，Bhalla M，Kanwar KJ．A comparative study of 20％azelaic acid cream monotherapy versus a sequential therapy in the treatment of melasma in dark- skinned patients．Dermatology 2000；205：249—254． [3 1]．Verallo-Rowell VM，Verallo V，Graupe K，et a1．Double-blind comparison of azelaic acid and hydroquinone in the treatment of melasma．Acne Derm Venereol Suppl(Stockh)1989；143：5 8·61． [32]．Lim JT．Treatment of melasma using kojic acid in a gel containing hydroquinone and glycolic acid．Dermatol Surg 1 999；25：282—284． [33]．Garcia A，Fulton JE．The combination of glycolic acid and hydroquinone or kojic acid for the treatment of melasma and related conditions．Dermatol Surg 1 996；22： 443．447． [34]．Zhu W，Gao J．The use of botanical extracts as topical skin-lightening agents for the improvement of skin pigmentation disorders．J Inv Dermatol Symp Proc． 2008；1 3：20-24． 【35]．Maeda K，Fukuda M．Arbutin：mechanism of its depigmenting action in human melanocytes culture．J Pharmacol Exp Ther 1996；276：765-769． 68 万方数据 Zhejiang University Master Thesis Literaturte review [3 6]．Funayama M，Arakawa H，Yamamoto R，et a1．Effects of alpha．and beta-arbutin on activity oftyrosinases from mushroom and mouse melanoma．Biosci Biotechnol Biochem 1 995；59：1 34． [3 71．Boissy RE，Visscher M，deLong MA．Deoxyarbutin：a novel reversible tyrosinase inhibitor with effective in—vivo skin lightening potency．Exp Dermatol 2005； 1 4： 601．608． [3 8]．Hakozaki T，Minwalla L，Zhuang J，et a1．The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer．Br J Dermatol 2002；147：20-31． [39]．Badreshia-Bansal S，Draelos Z．Insight into skin lightening cosmeceuticals for women of Color．J Drugs Dermatol 2007；6：32—39． [40]．Bissett DL，Miyamoto K，Sun P，et a1．Topical niacinamide produces yellowing， wrinkling，red blotchiness，and hyperpigmented spots in aging facial skin．Int J Cosmet Sci 2004；26：231-238． [4 1]．Kimball AB，Kaczvinsky JR，Li j，et a1．Reduction in the appearance of facial hyperpigmentation after use of moisturizers with a combination of topical niacinamide and N-acetyl glucosamine：results of a randomized，double．blind， vehicle—controlled trial．Br J Dermat01．Aug 28，2009．[Epub ahead of print]． [42]．Bissett DL，Robinson LR，Raleigh PS，et a1．Reduction in the appearance of facial hyperpigmentation by topical N—acetyl glucosamine．J Cosmet Dermatol 2007；6： 20．26． [43]．Farris，PK．Topical vitamin C：a useful agent for treating photoaging and other dermatologic conditions．Derrnatol Surg 2005；3 1：814—818． [44]．Shindo Y，Witt E，Hans D，et a11．Enzymic and non—enzymic antioxidants in the epidermis and the dermis ofhuman skin．J Invest Dermatol 1994；102：122．124． [451．Lin JY，Selim MA，Shea CR，et a1．UV photoprotection by combination topical antioxidants vitamin C and vitamin E．J Am Acad Dermatol 2003；48：866．874． [46]．Kobayashi S，Takehana M，Itoh S，et a1．Protective effect of magnesium．L． ascorbyl-2-phosphate against skin damage induced by UVB radimion．Photochem Photobiol 1 996；64：224．228． 69 万方数据 Zhejiang University Master Thesis Literaturte review [47]．Carcamo JM，Pedraza A．Borquez—oj eda O，et a1．Vitamin C suppresses TNF alpha-induced NF kappa B activation by inhibiting I kappa B alpha phosphorylation．Biochemistry 2002；41：12995—30002． [48]．Perricone NV．The photoprotective and anti—inflammatory effects of topical ascorbyl palmitate．J Geriatr Dermatol 1 993；1：5—1 0． [49]．Espinal—Perez LE，Moncada B，Castanedo—Cazares JP．A double-blind randomized trial of 5％ascorbic acid VS．4％hydroquinone in melasma．Int J Dermatol 2004；43： 604．607． [50]．Kameyama K，Sakai C，Kondoh S，et a1．Inhibitory effect of magnesium L— ascorbyl一2一phosphate(VC-PMG)on melanogenesis in vitro and in vivo．J Am Acad Dermatol 1996；34：29—33． [5 1]．Asl MN，Hosseinzadeh H．Review of pharmacological effects of Glycyrrhiza sp． and its bioactive compounds．Phytother Res 2008；22：709-724． [52]．gmer M，Metwalli M．Topical liquiritin improves melasma．Intl J Dermatol 2000； 39：299—301． [53]．Paine C，Sharlow E，Liebel F，et a1．An altemative approach to depigmentation by soybean extracts via inhibition of the PAR-2 pathway．J Invest Dermatol 200 1；1 1 6： 587．595． [541．Wallo W，Nebus J，Leyden JJ．Efficacy of a soy moisturizer in photoaging：a double—blind，vehicle—controlled，1 2一week study．J Drugs Dermatol 2007；6：9 1 7— 922． [55]．Hermanns JF，Petit L，Pierard—Franchimont C，et a1．Assessment of topical hypopigmenting agents on solar lentigines of Asian women．Dermatology 2002； 204：281．286． [561．Finkey MB，Hemdon J，Stephens T，et a1．Soy moisturizer SPF 15 improves dyschromia[Poster]．J Am Acad Dermatol 2005；52(Suppl)：P25． [57]．Sah A，Stephens TJ，Kurtz ES．Topical acne treatment improves postacne inflammatory hyperpigmentation(PIH)in skin of color[Poster]．J Am Acad Dermatol 2005；52(Suppl)：P25 70 万方数据 Zhejiang University Master Thesis Literaturte review [58]．Sarkar M．Medium-depth chemical peels and deep chemical peels．In：Grimes PE， ed．Aesthetics and Cosmetic Surgery for Darker Skin Types．Philadelphia,PA： Lippincott Williams&Wilkins；2008：1 54—1 69． [5 9]．Grimes PE，Rendon MI，Pellerano J．Superficial chemical peels．In：Grimes PE，ed． Aesthetics and Cosmetic Surgery for Darker Skin Types．Philadelphia，PA： Lippincott Williams&Wilkins；2008：154-169． [60]．Roberts WE．Chemical peeling in an ethnic／dark skin．Dermatol Ther 2004；1 7： 196．205． [6 1]．Leu D，Yoo S S．Epidermal and color improvement in ethnic skin： microdermabrasion and superficial peels．In：Alam M，Bhatia AC，Kundu RV，Yoo SS，Chan HH，eds．Cosmetic Dermatology for Skin of Color．New York，NY： McGraw Hill；2009：29—33． [62]．Song JY，Kang HA，Kim MY，et a1．Damage and recovery of skin barrier function after glycolic acid chemical peel and crystal microdermabrasion．Dermatol Surg 2004；30：390—394． [63]．Bums RL，Prevost—Blank PL，Lawry MA，et a1．Glycolic acid peels for postinflammatory hyperpigmentation in black patients：a comparative study． Dermatol Surg 1997；23：171-174． [64]．Ahn HH，Kim IH．Whitening effect of salicylic acid peels in Asian in patients． Dermatol Surg 2006；32：372—375． [65]．Grimes PE．The safety and efficacy of salicylic acid peels in darker racial—ethnic groups．Dermatol Surg 1 999；25：1 8—22． [66]．zj az A，Raza N，Iftikhar N，et a1．Comparison of 3 0％salicylic acid with Jessner’S solmion for superficial chemical peeling in epidermal melasma．J Coll Physicians Surg Pak 2008；1 8：205-208． [67]．Nanda S，Grover C，Reddy BS．Efficacy of hydroquinone(2％)versus tretinoin (0．25％)as adjunct topical agents for chemical peeling in patients of melasma． Dermatol Surg 2004；30：385-388． [68]．Antoniou C，Stefanaki C．Cosmetic camouflage．J Cosmet Dermatol 2006；5：297- 301． 万方数据 Zhejiang University Master Thesis Literaturte review [69]．Holme SA，Beattie PE，Fleming CJ．Cosmetic camouflage advice improves quality of life．Br J Dermatol 2002；1 47：946—949． [70]．Kent G．Testing a model of disfigurement：effects of a skin camouflage service on well—being and appearance anxiety．Psych01 Health 2002；17：377—386． [71]．Tanioka M，Miyachi Y．Camouflage for vitiligo．Dermatolog Ther 2009；22：90—93． [72]．Robe,s NG，Nordlund JJ，WrieSt C．The corrective cover or camouflage clinic． Ear Nose Throat J 1 989；68：480-482． [73]．Rayner VL．Camouflage therapy．Dermatol Clin 1995；13：467．472． [74]．Alster TS，Tartzi EL．Laser surgery in dark skin．SKINmed 2003；2：80-85． [75]．Battle EF，Hobbs LM．Laser therapy on darker ethnic skin．Dermatol Clin 2003；2 1： 713．723． [76]．Katz TM，Goldberg LH，Firoz BF，et a1．Fractional photothermolysis for the treatment of postinflammatory hyperpigmentation．Dermatol Surg 2009；3 5：1 844— 1848． [77]．Terrell S，Aires D，Schweiger ES．Treatment of acne vulgaris using blue light photodynamic therapy in African-American patients．J Drugs Dermatol 2009；8： 669．671． [78]．Cho SB，Park SJ，Kim JS，et a1．Treatment of postinflammatory hyperpigmentafion using 1 064一nin Q—switched Nd：YAG laser with low fluence：report of three cases．J Eur Acad Dermatol Venereol 2009；23：1 206- 1 207． [79]．Wang CC，Hui CY，Sue YM，et a1．Intense pulsed light for the treatment of refractory melasma in Asians persons．Dermatol Surg 2004；30：1 96—200． [80]．Katz TM，Goldberg LH，Firoz BF，et a1．Fractional photothermolysis for the treatment ofpostinflammatory hyperpigmentation．Dermatol Surg 2009；35：1844— 1848． [8 1]．Hantash BM，Bedi VP，Chan KF，et a1．Ex vivo histological characterization of a novel ablative fractional resurfacing device．Lasers Surg Med 2007；39(2)：87．95． 72 万方数据 Zhejiang University Master Thesis 作者简历 作若筒硒 个人信息 姓名：Clarissa Dwipuspa Wij aya 中文名：黄小芳 联系电话：+86 1 8520737457 E—mail：shazal 508@hotmail．com 籍贯：巨港，印度尼西亚 性别：女 主要要求学经历 2007．09．2012．02 苏州大学医学院，MBBS program 2012．02．2013．02 苏州大学附属第一医院实习生 2013．09．2014．02 浙江大学医学院硕士研究生专业学位 2014．02．2016．05 浙江大学医学院附属邵逸夫医院实习轮转 万方数据