Melasma: A comprehensive update Part I
Abstract
摘要
英文原文
Melasma is a common disorder of hyperpigmentation affecting millions of people worldwide. While it is thought to be triggered or exacerbated by sun exposure and hormones, much remains to be understood about its pathogenesis. A thorough understanding of the etiology of melasma and the research tools available to study this condition are crucial to enhancing management and developing novel targeted therapies of this often frustrating condition.
对应中文
黄褐斑是一种常见的色素沉着疾病，影响着全世界数百万人。虽然它被认为是由阳光照射和激素引起或加剧的，但对其发病机制仍有待进一步了解。深入了解黄褐斑的病因和研究其可行的工具，对于加强管理和开发这种常见疾病的新型靶向疗法至关重要。
Introduction
引言
英文原文
Melasma is a common disorder of hyperpigmentation that affects more than 5 million people in the United States alone.Found most commonly in women with Fitzpatrick skin phototypes III through V living in areas of intense ultraviolet (UV) light exposure, melasma is often difficult to treat and has a significant negative impact on patients’ quality of life.The avoidance of exacerbating factors such as UV light and hormonal contraceptives and testing for underlying thyroid disorders can lead to improvement in certain subsets of patients. Recent studies, however, have shown that the underlying basis for melasma may be more complex than originally thought. These findings also provide new avenues for research into better understanding and treating this challenging condition.
对应中文
黄褐斑是一种常见的色素沉着疾病，仅在美国就有500多万人受其影响。黄褐斑最常见于生活在强紫外线(UV)照射区域的菲茨帕特里克皮肤III~V型女性，通常难以治疗，对患者的生活质量有显著的负面影响。避免病情恶化的因素，如紫外线照射和激素避孕药，以及检测潜在的甲状腺疾病，可以改善某些亚群患者的病情。然而，最近的研究表明，黄褐斑的根本机制可能比最初的发现更复杂。这些发现也为更好地理解和治疗这种具有挑战性疾病的研究提供了新的途径。
英文原文
Melasma is an acquired disorder of symmetrical hyperpigmentation appearing as light brown to dark, muddy brown macules and patches on the face, especially the forehead, malar areas, and chin. It is also sometimes referred to as chloasma or the mask of pregnancy, a term used in the dermatology literature for several decades. The term chloasma comes from the Greek chloazein, meaning to be green, whereas the term melasma comes from the Greek melas, meaning black.
对应中文
黄褐斑是一种获得性的对称性色素沉着疾病，表现为面部浅褐色至深褐色的斑点和斑块，尤其是额头、颧骨和下巴。它有时也被称为“chloasma”或“the mask of pregnancy”，这是皮肤病文献中用来表示几种疾病的术语。术语“chloasma”一词源于希腊语chloazein，意思是绿色，而术语“melasma”一词源于希腊语melas，意思是黑色。
CAPSULE SUMMARY
简要
英文原文
· Melasma is a common disorder of hyperpigmentation found in all parts of the world that significantly affects quality of life; it is exacerbated by sun exposure and hormonal factors, making photoprotection and avoidance of trigger factors a critical part of management.
· Recently identified pathogenic factors include stem cell factor and c-kit along with neural and vascular growth factors.
· An increased understanding of the etiology of melasma will aid in the development of novel therapies.
对应中文
– 黄褐斑是一种常见的色素沉着疾病，在世界各地都有发现，严重影响人们生活质量；阳光照射和激素因素会加剧病情，因此光保护和避免触发因素是管理疾病的关键部分。
– 最近发现的致病因素包括干细胞因子和神经、血管生长因子受体。
– 进一步了解黄褐斑病因学将有助于开发新的治疗方法。
EPIDEMIOLOGY
流行病学
Key points
要点
英文原文
· The reported prevalence of melasma ranges from 8.8% among Latino females in the Southern United States to as high as 40% in Southeast Asian populations
· Melasma predominantly affects Fitzpatrick skin phototypes III and IV and often lasts for many years after pregnancy
对应中文
– 据报道，黄褐斑的发病率从美国南部拉丁裔女性的8.8%到东南亚人群的40%不等。
– 黄褐斑主要影响菲茨帕特里克皮肤III型和IV型人群，并经常在怀孕后持续多年。
英文原文
Several studies from around the world have attempted to discern the prevalence of melasma in the general population; however, few have randomly sampled the general population. In a randomized study involving self-reporting of melasma in a Hispanic female population in Texas, Werlinger et al noted the prevalence to be 8.8%, with an additional 4% reporting melasma in the past. In Southeast Asia, the prevalence has been reported to be as high as 40% in females and 20% in males; however, these were patients presenting to a dermatology clinic, indicating some ascertainment bias. A survey of Arab Americans living in the United States found that melasma was the fifth most commonly reported skin condition,mentioned by 14.5% of people surveyed. A recent multicenter survey of females from nine countries found that Fitzpatrick skin phototypes III and IV were most commonly affected, and that African Americans were more likely to have a positive family history of melasma. It was also noted that 41% of women surveyed had onset of disease after pregnancy but before menopause. Importantly, only 8% noted spontaneous remission. Only 25% of patients taking oral contraceptives had an onset of melasma after starting their contraceptive. While melasma was thought to be a pregnancy and contraceptive-related disorder in the past, recent studies show that in many patients it is a chronic disorder that may last for decades. Although common, there is much to learn about the epidemiology of melasma worldwide.
对应中文
一些在世界各地的研究试图识别在普通人群中黄褐斑的患病率；然而，很少有人对普通人群进行随机抽样。在一项随机研究中，Werlinger等人指出，在德克萨斯州的西班牙裔女性人口中，黄褐斑患病率为8.8%，另外有4%的人在过去表示患有黄褐斑。在东南亚，有报告称女性的患病率高达40%，男性为20%；然而，这些患者到皮肤科诊所就诊，表明存在一些确认偏差。一项针对居住在美国的阿拉伯裔美国人调查发现，第五大最常见的皮肤疾病是黄褐斑，14.5%的受访者提到了这一点。最近一项对9个国家女性的多中心调查发现，菲茨帕特里克皮肤III型和IV型最常受到黄褐斑影响，非裔美国人更有可能有黄褐斑的家族史。调查还指出，41%的受访女性在怀孕后、绝经前发病。重要的是，只有8%的患者发现病情自行缓解。只有25%的口服避孕药患者在开始服用避孕药后出现黄褐斑。虽然过去认为黄褐斑是一种与怀孕和避孕有关的疾病，但最近的研究表明，在许多患者中，它是一种可能持续数十年的慢性疾病。虽然黄褐斑很常见，但在世界范围内仍有许多关于黄褐斑的流行病学需要了解。
CLINICAL AND PATHOLOGIC FEATURES
临床和病理特征
Key points
要点
英文原文
· The centrofacial pattern of melasma is the most common
· While a Wood lamp examination was previously thought to accurately predict epidermal versus dermal pigment deposition, recent studies have shown that dermal melanin deposition is common and may be underrecognized
· Melasma may be caused by the presence of more biologically active melanocytes in the affected skin, rather than an increase in melanocytes
对应中文
– 黄褐斑以面部中心区模式最为常见
– 虽然以前认为木灯皮肤检查可以准确预测表皮与真皮的色素沉积，但最近的研究表明，皮肤黑色素沉积很常见，而且可能没有被充分认识到
– 黄褐斑可能是由于病损皮肤中存在更多的生物活性黑素细胞，而不是黑素细胞的增加
CLINICAL AND PATHOLOGIC FEATURES
临床和病理特征
英文原文
Several clinical patterns of melasma have been described, but many patients have a mixture of these patterns. The centrofacial pattern is the most common and consists of lesions on the forehead, cheeks, nose, upper lip, or chin. The malar pattern describes lesions located primarily on the cheeks and nose. The mandibular pattern consists of lesions on the ramus of the mandible. This latter pattern may actually be a form of poikiloderma of Civatte, because patients are often postmenopausal and biopsy specimens reveal significant actinic damage. Although melasma of the forearms has been described, this entity is not always present in patients with facial melasma and has not been well characterized.Melasma can be further classified based on a Wood lamp examination to help identify the location of the pigment. Lesions that are enhanced when viewed under a Wood lamp imply increased epidermal melanin content, whereas those that are not enhanced with a Wood lamp examination imply an increase in dermal melanin content. Lesions that have both enhancing and nonenhancing areas are said to have a mixed pattern. Recent histologic studies indicate that this construct may not be accurate.
对应中文
既往已经描述过黄褐斑的几种临床模式，但许多患者都是这些模式的混合。面部中心型是最常见的，由额头、脸颊、鼻子、上唇或下巴的病变组成。颧骨模式描述的病变主要位于脸颊和鼻子。下颌骨模式由下颌骨分支的病变组成。后一种模式实际上可能是西瓦特皮肤异色病的一种形式，因为患者往往绝经后，活检标本显示出明显的光损伤。虽然前臂黄褐斑已被描述，但在面部黄褐斑患者身上并不总是出现这种情况，并且它没有很明显的特征。黄褐斑可以根据木灯皮肤检查进一步分类，以帮助确定色素的位置。在木灯下观察时，病变增强意味着表皮黑色素含量增加，而那些没有增强的病变意味着真皮黑色素含量增加。既有增强区又有非增强区的病变被称为混合型。最近的组织学研究表明，这种结构可能并不准确。
英文原文
Few histopathologic studies have been performed on melasma, but several recent publications have provided new insight into its pathogenesis. A study by Sanchez et al examined biopsy specimens of lesional skin. The authors found two basic patterns of melasma: an epidermal form that featured melanin deposition mainly in the basal and suprabasal layers and melanocytes that were highly dendritic and full of pigment, and a dermal form with superficial and deep perivascular melanophages in the dermis with noticeably less prominent epidermal pigmentation. Electron microscopy revealed highly melanized stage IV melanocytes in lesional skin. Importantly, a Wood lamp examination of lesional skin correlated with the results of the biopsy; that is, patients who were judged to have epidermal melasma clinically also had prominent epidermal hyperpigmentation on light microscopic examination. Expanding on this work, Grimes et al studied patients with Fitzpatrick skin phototypes IV through VI with epidermal and mixed melasma by Wood lamp examination and examined biopsy specimens both from lesional skin and nearby normal-appearing skin. Unlike previous studies, they found that despite a Wood lamp evaluation indicating epidermal melasma in some patients, all samples examined had increased melanin deposition in the epidermis and dermis. They further used Mel-5 staining to show that there was no increase in melanocyte number, but the melanocytes themselves were larger and had more prominent dendritic processes. This last finding was confirmed with electron microscopy. Therefore, patients with apparent epidermal melasma after a Wood lamp examination may have significant melanin in the dermis.
对应中文
很少有人对黄褐斑进行组织病理学研究，但最近的几篇文章为其发病机制提供了新的见解。Sanchez等人的一项研究检查了病变皮肤的活检标本。作者发现了两种基本的黄褐斑模式：一种是表皮形态，其特点是黑色素主要沉积在基底层和基底上层，黑色素细胞高度树枝状并充满色素；另一种是真皮形态，其浅层和深层血管周围有嗜黑色素细胞，表皮色素沉着明显较少。电子显微镜显示，病变皮肤中有高度黑素化的IV期黑色素细胞。重要的是，病变皮肤的木灯皮肤检查与活检结果相关；也就是说，临床上判断为表皮黄褐斑的患者，光镜检查也有明显的表皮色素沉着。在这项工作的基础上，Grimes等人通过木灯皮肤检查对菲茨帕特里克皮肤光型IV至VI伴有表皮和混合性黄褐斑的患者进行研究，并对病损皮肤和附近正常皮肤的活组织标本进行检查。与以前的研究不同，他们发现尽管木灯皮肤检查评估表明一些患者患有表皮黄褐斑，但所有被检查的样本，表皮和真皮中的黑色素沉积明显增加。他们进一步用Mel-5染色显示，黑色素细胞数量没有增加，但黑色素细胞本身变大，并有更突出的树突。最后一项发现被电子显微镜证实。因此，木灯皮肤检查发现有明显表皮黄褐斑的患者可能在真皮层有明显的黑色素。
英文原文
A similar study by Kang et al evaluated the histopathologic characteristics of melasma skin compared to nearby normal-appearing skin in Asian patients, showing that melasma skin had more severe solar elastosis, a greater number of epidermal melanocytes, more dermal free melanin and melanophages, and significantly increased melanin in all layers of the epidermis. Interestingly, there was no difference in the number of Langerhans cells, appearance of the basement membrane, or collagen between the involved and uninvolved areas; however, there was increased elastic fiber fragmentation in the melasma skin. Furthermore, melanocytes in melasma skin had more dendrites, mitochondria, Golgi, and rough endoplasmic reticulum, suggesting that they were more biologically active than their counterparts in normal skin. The presence of dermal melanin and melanophages in these studies may explain the difficulty in treating patients with appar- ent epidermal melasma.
对应中文
一项Kang等人的类似研究评估了亚洲患者黄褐斑皮肤的组织病理学特征，并将其与附近的正常皮肤进行了比较，结果显示黄褐斑皮肤有更严重的日光性弹性组织变性、表皮黑色素细胞更多、更多真皮游离黑色素和嗜黑色素细胞，表皮各层的黑色素显著增加。有趣的是，病损区和未病损区在朗格汉斯细胞数量、基底膜外观或胶原蛋白方面没有差异；然而，黄褐斑皮肤弹性纤维断裂增加。此外，黄褐斑皮肤中的黑色素细胞有更多的树突、线粒体、高尔基体和粗糙的内质网，这表明它们比正常皮肤中的黑色素细胞更具有生物活性。在这些研究中，真皮黑色素和嗜黑色素细胞的存在可能解释了治疗表皮性黄褐斑患者的困难。
ETIOPATHOGENESIS
病因
Key points
要点
英文原文
· The high incidence of melasma among family members suggests a genetic component
· Sun exposure is a commonly reported exacerbating factor, likely because of the UV-induced upregulation of melanocyte stimulating cytokines
· While melasma is known to occur with hormonal changes, clinical evidence to date does not clearly associate serum hormone levels to melasma
· For women who note the onset of melasma after beginning a course of an oral contraceptive, the medication should be stopped if possible
对应中文
– 黄褐斑在家庭成员中的高发病率表明有遗传因素
– 阳光暴露是一种常见的恶化因素，可能是因为紫外线诱导黑素细胞刺激性细胞因子上调
– 虽然已知黄褐斑会随着激素变化而发生，但迄今为止的临床证据并没有明确地将血清激素水平与黄褐斑联系起来
– 对于在开始使用口服避孕药后出现黄褐斑的妇女，应尽可能停止服药
英文原文
While the exact underlying etiology for melasma remains a mystery, several well known risk factors exist. Melasma is more common in darker skin types, particularly Fitzpatrick skin types III and IV. Other reported risk factors include genetic predisposition, exposure to ultraviolet light, pregnancy, and exogenous hormones (ie, oral contraceptives and hormone replacement therapy). A genetic predisposition is suggested by a high reported incidence in family members in several studies. An Iranian survey of pregnant women with melasma reported a 54.7% incidence of melasma in a family member. A similar study from Singapore revealed a positive family history of melasma in 10.2% of study subjects, and in Latino men, Vasquez et al found a positive family history in 70.4% of study subjects. Forty-eight percent of 324 women in a global survey reported a family history of melasma.
对应中文
虽然黄褐斑确切潜在病因仍然是个谜，但存在几个众所周知的风险因素。黄褐斑在深色皮肤类型中更常见，特别是菲茨帕特里克皮肤III型和IV型。其他报告的风险因素包括遗传易感性、暴露于紫外线、怀孕和外源性激素(即口服避孕药和激素替代疗法)。在一些研究中，家族成员高发病率表明有遗传倾向。伊朗一项对患有黄褐斑孕妇的调查报告显示，家庭成员中黄褐斑发生率为54.7%。新加坡的一项类似研究显示，10.2%的研究对象有黄褐斑的阳性家族史，而Vasquez等人发现在拉丁裔男性中70.4%的研究对象有阳性家族史。在一项全球调查中，324名妇女中有48%报告有黄褐斑的家族史。
英文原文
UV light is a commonly reported initiating or exacerbating factor for melasma, likely because of its effects on melanocytes and on cytokine production. Melasma occurs in sun-exposed areas, and many patients report an increased severity of melasma with sun exposure. One reason for this appears to be that UV radiation induces melanocyte proliferation, migration, and melanogenesis. In addition, UV radiation can lead to the production of multiple cytokines, including interleukin-1, endothelin-1, alphaemelanocyte-stimulating hormone (a-MSH), and adrenocorticotropic hormone (ACTH) from keratinocytes, which in turn upregulate melanocyte proliferation and melanogenesis. Examining the local expression of cytokines in lesional and perilesional skin from 10 Korean women, Im et al used immunohistochemistry to show that a-MSH was expressed to a greater degree in lesional melasma skin in the stratum spinosum and stratum granulosum than in perilesional skin. There was, however, no difference in the amount of melanocortin-1 receptor or ACTH expression. These findings suggest that sustained overexpression of MSH in lesional skin after UV exposure may be a significant factor for the development of melasma.
对应中文
据报道，紫外线是引发或加重黄褐斑的常见因素，可能是因为它对黑色素细胞和细胞因子的产生有影响。黄褐斑发生在阳光暴晒的地方，许多患者报告说，随着阳光照射，黄褐斑的严重程度增加。其中一个原因似乎是紫外线辐射诱导黑色素细胞的增殖、迁移和黑色素生成。此外，紫外线辐射可导致多种细胞因子的产生，包括白介素1、内皮素1、α-黑色素细胞刺激素(a-MSH)和肾上腺皮质激素(ACTH)，进而促进黑色素细胞的增殖和黑色素生成。Im等人用免疫组化技术检测了10例韩国女性病损及病损周围皮肤中细胞因子的局部表达，发现α-MSH在黄褐斑病损皮肤的棘层和颗粒层的表达高于病损周围皮肤。然而，黑素皮质素受体1或肾上腺皮质激素的表达数量没有差异。这些发现表明，紫外线照射后病变皮肤中黑色素细胞刺激素持续过度表达可能是黄褐斑发生的一个重要因素。
ETIOPATHOGENESIS
发病机制
Key points
要点
英文原文
Finally, melasma may also have a vascular component in its pathogenesis. Kim et al found that biopsy specimens of lesional melasma skin had greater vascular endothelial growth factor expression in keratinocytes compared to nearby nonlesional skin. Factor VIIIerelated antigen staining showed that melasma skin had more numerous and larger blood vessels compared to uninvolved skin. Furthermore, using tristimulus colorimetry specifically measuring redegreen wavelengths, the authors found that involved skin had higher values for this variable, implying that the clinical observation of increased vascularity correlates with histopathologic findings.
对应中文
最后，黄褐斑的发病机制也可能与血管有关。Kim等人发现，与附近的非病变皮肤相比，黄褐斑病变皮肤的活检标本中角质细胞中的血管内皮生长因子表达更强。第八因子相关抗原染色显示，与正常皮肤相比，黄褐斑皮肤有数量更多、体积更大的血管。此外，通过专门测量红绿色波长的三色刺激比色法，作者发现病损皮肤的这一变量值更高，这意味着临床观察到增加的血管与组织病理学发现相关。
英文原文
In summary, there appears to be a complex interplay of hormonal and environmental factors that predispose certain patients to developing melasma. The presence of local hormones in the skin may play a greater role than originally thought. While the exact link between hormones and melasma is not clear, it is recommended that patients who develop melasma while taking an oral contraceptive should stop the medication when possible. Additional work in this area is needed to help elucidate the underlying pathogenesis of this condition.
对应中文
综上所述，激素和环境因素之间复杂相互作用使某些患者容易患上黄褐斑。皮肤中局部激素的存在可能比原先认为所产生的影响更大。虽然激素和黄褐斑之间的确切联系尚不清楚，但建议口服避孕药期间出现黄褐斑的患者应尽可能停止用药。这一领域需要进行更多的工作，以帮助阐明这一疾病的潜在发病机制。
Differential diagnosis
鉴别诊断
英文原文
Disorders that can be confused for melasma include postinflammatory hyperpigmentation, solar lentigines, ephelides, drug-induced pigmentation, actinic lichen planus, facial acanthosis nigricans, frictional melanosis, acquired bilateral nevus of Otaelike macules (Hori’s nevus), and nevus of Ota.These can sometimes coexist in patients with melasma, making distinction important when devising treatment plans or enrolling patients for clinical trials. A careful medial history, an examination of the skin including a Wood lamp examination, the recognition of concomitant inflammatory disorders, and a skin biopsy specimen are all helpful in making the correct diagnosis.
对应中文
与黄褐斑容易混淆的疾病可能包括炎症色素沉着、日光性雀斑样痣、雀斑、药物引起的色素沉着、扁平苔藓、面部黑棘皮病、摩擦性黑变病、颧部褐青色斑和太田痣。这些疾病有时可与黄褐斑同时存在，在制定治疗计划或招募患者进行临床试验时，区分这些疾病非常重要。仔细了解病史，对皮肤进行检查，包括木灯皮肤检查，识别合并的炎症疾病，以及皮肤活检标本，都有助于做出正确的诊断。
QUALITY OF LIFE STUDIES: MEASURING THE IMPACT OF MELASMA
生活质量研究:测量黄褐斑的影响
Key points
要点
英文原文
· Validated questionnaires in several populations have shown that even a small amount of melasma can cause significant emotional and psychological distress
· Patients with lower levels of education or underlying psychiatric disorders may be at greater risk of emotional impairment
对应中文
·在对一些人群进行的问卷调查表明，即使是少量的黄褐斑也会导致严重的情绪和心理困扰
·教育水平较低或有潜在精神障碍的患者可能有更高的情绪障碍风险
英文原文
Melasma is often psychologically distressing in affected patients. The most commonly used tool for assessment of quality of life in patients with melasma is the MelasQoL. This questionnaire was developed by modifying items from the SKINDEX-16 and skin discoloration questionnaire. By surveying 102 women with melasma, the authors found that the areas most impacted by the disease were social life, recreation/leisure, and emotional well being. These results correlated well with results from the SKINDEX-16 and the Dermatology Life Quality Index (DLQI) questionnaires, validating the MelasQoL. Interestingly, the effect of melasma on quality of life was not correlated with the severity of melasma, suggesting that even a small amount of pigmentation can take a significant emotional toll. The benefit of the MelasQoL is that it does not weigh physical and psychological distress equally, which is important for disorders of pigmentation, which lack scaling, pruritus, pain, and other types of physical impairment. This questionnaire has since been translated into Spanish and Portuguese and thus far has been shown to be readily adaptable to other cultures. In the Spanish version, patients with little to no education were found to have higher scores, indicating greater emotional and psychological burdens of disease in this subset of patients, while the Portuguese study found higher scores in patients with underlying psychiatric disorders. It is clear that melasma significantly affects quality of life, and its effect on a particular patient may be profound.
对应中文
黄褐斑常常影响患者使其引起心理上的痛苦。最常用于评估黄褐斑患者生活质量的工具是MelasQoL。该问卷是通过修改SKINDEX-16和皮肤变色问卷的项目而开发的。通过对102名患有黄褐斑的妇女进行调查，作者发现，受疾病影响最大的领域是社会生活、娱乐/休闲和情感生活。这些结果与SKINDEX-16和皮肤病生活质量指数（DLQI）问卷调查的结果有相关性，验证了MelasQoL问卷。有趣的是，黄褐斑对生活质量的影响与黄褐斑的严重程度无关，这表明即使少量的色素沉着也会对情绪造成重大影响。MelasQoL的优势在于，不对身体和心理上的痛苦进行同等权衡，这对缺乏脱屑、瘙痒、疼痛和其他类型身体损伤的色素沉着症来说很重要。这个问卷后来被翻译成西班牙文和葡萄牙文，到目前为止，已经证明问卷可以很容易地融入到其他文化中使用。在西班牙语版本中，发现受教育程度低或没有受教育程度的患者得分较高，表明黄褐斑对这部分患者的情绪和心理影响更大，而葡萄牙语研究发现有潜在精神障碍的患者得分更高。很明显，黄褐斑严重影响了人们的生活质量，它对特定患者可能有深远的影响。
英文原文
Melasma involves a complex interaction of environmental, hormonal, and cellular factors, and new research has increased our understanding of this disease—but much work still needs to be done. Additional studies to understand the genetic pathways that trigger melasma and to identify the roles of cellular growth factors in the pathogenesis of melasma are needed, because these may serve as new targets for therapy. In addition, the role of hormones in initiating or exacerbating melasma still needs to be better clarified. Given the impact that this condition has on patients’ quality of life and the lack of highly effective treatment options, additional research into understanding the biologic basis of this disease will be crucial to developing more effective treatment options.
对应中文
黄褐斑涉及环境、激素和细胞因素之间复杂的相互作用，新的研究增加了我们对这种疾病的了解—但仍有许多工作需要做。我们需要进行更多的研究来了解引发黄褐斑的遗传途径，并确定细胞生长因子在黄褐斑发病机制中的作用，因为这些可能成为治疗疾病的新方向。此外，需要更好地阐明激素在引发或加剧黄褐斑方面的作用。鉴于这种疾病影响患者生活质量以及缺乏高效治疗方案，进一步研究了解这种疾病的生物学基础将对开发更有效的治疗方案至关重要。
REFERENCES
1.Sheth, V. M., & Pandya, A. G. (2011). Melasma: a comprehensive update: part I.Journal of the American Academy of Dermatology,65(4), 689–697.