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INTRODUTION 引言 Acne vulgaris is a common, chronic inflam-matory skin disease that affects mainlyadolescents and young adults. There is a wide variety of acne treatments, which reflects the complex and multifactorial pathogenesis of acne. Conventional therapies such as ret-inoids, benzoyl peroxide and antibiotics are the cornerstone for acne treatment. How-ever, these therapies may not be effective in some cases, leading to refractory acne. In addition,propionibacterial resistance toantibiotics has been increasing over the last years,leading to the constant changing of the guidelines for acne management.Furth-ermore,cutaneous and systemic side effects including birth defects are important issue-s stemming from the use of oral isotretinoin.Therefore, alternative treatments are be-ing studied. 寻常型痤疮是一种常见的, 慢性炎症型皮肤病，常发于青少年和年轻人。痤疮发病机制的复杂性和多因素性导致痤疮治疗的多样化。常规治疗方法，例如维A酸，过氧化苯甲酰和抗生素是痤疮治疗的基本药物。但是，在一些难治性痤疮的病例中，这些治疗方法可能无效。此外，过去几年中，丙酸杆菌对抗生素的抗药性持续增加，使痤疮治疗的指南不断变化。再者，因口服异维A酸，产生的皮肤和全身副作用，包括先天畸形，这些都是重大的问题。因此，我们正研究其他替代性治疗方法。 Light therapies suchas photodynamic thera-py (PDT) have been taking an important pla-ce in dermatological practices. These procedures may offer alternatives to people who seek topical treatments, quicker onset of action, non-serious side effects and decreased antibiotic resistance rates. 在皮肤病学实践中，光疗法，例如光动力治疗（PDT）已占有重要地位。对于寻求局部治疗，起效快，无严重副作用，抗生素耐药率降低的患者而言，光疗法可能会为他们提供替代治疗方法。 The use of light therapy comes from the fact that Propionibacterium acnes, anaerobic and commensalbacteria on human skin produce endogenous porphyrins,particularly coproporphyrin III (CPIII).Porphyrins may contribute to the inflammatory reaction by producing cytotoxic effects in the sebaceous glands. Onthe other hand, benefits from the photosensitizing effect of endogenous porphyrins have been described with exposures to blue and/orred light sources. These studies have been shown to reduce 49-75% of inflammatory lesions in treated patients versus 10-25% in untreated patients. Also, acne can respond well to photodynamic therapy using topical porphyrin precursors such as 5-aminolaevulinic acid (ALA) or methyl aminolevulinate (MAL). Photoactivated porphyrins produce the formationof singlet oxygen and other potent oxidizers that induce transient antimicrobial and anti-inflammatory effects. Moreover, red light ALA-PDT has been proven to cause a direct photodynamic destruction of sebaceousglands and then long-term remission of acne. Even though MAL-PDT has been shown to be as effective as antibiotics with a 68% reduction in the number of inflammatory lesions, there is little information comparing the efficacy of red light alone and MAL-PDT treatment. 人体皮肤内痤疮丙酸杆菌、厌氧菌和共生菌产生内源性卟啉，特别是粪卟啉Ⅲ（CPIII），它们对皮脂腺会产生细胞毒性效应，并可能造成炎症反应。光疗法的治疗原理就是针对以上病因（让卟啉分解）。另一方面，有报道指出：在红蓝光源照射下，由于内源性卟啉的光敏效应导致其分解，因此可以让患者受益。这些研究表明，相对于未经治疗的患者，光疗法后其炎性皮损减少了10-25%，而在已接受治疗的患者中，其炎性皮损减少了49-75%。并且，运用局部卟啉前体【例如5-氨基乙酰丙酸（ALA）或者甲基氨基乙酰丙酸（MAL）】的光动力治疗对痤疮疗效良好。光活化卟啉形成单线态氧和其他强效氧化剂，这些形成物会诱发短暂的抗菌和抗炎效果。而且，红光ALA-PDT已被证实对皮脂腺有直接的光动力杀伤作用，进而可以长期缓解痤疮。尽管MAL-PDT和抗生素有同样疗效，炎性皮损数量都减少了68%，但单色红光和MAL-PDT疗效的对比资料几乎没有。 Therefore, our aim wasto compare the efficacy and tolerability of red light alone and MAL-PDT inpatients with mild to moderate facial acne. In addition, we investigated the pattern of treatment response for each treatment. 因此，本文旨在比较单色红光和MAL-PDT这两种治疗方法对轻度至中度面部痤疮患者的有效性和耐受性。此外，我们对患者每次的治疗反馈模式也做了研究。 DISCUSSION 讨论 This study shows thatred light MAL-PDT treatment has a rapid onset of action. At week 2, 82.3% of the patients with grade II-IV achieved grade 0-I. Also, the median of inflammatory lesions decreased from 52 to 5 with a median percent reduction of 91.3%. In contrast, only 14.2% of the patients with grade II-IV achieved grade 0-I in the red light alone group. However, both treatments were significantly effective for improving inflammatory and non-inflammatory lesions. Interestingly, patients from the red light alone group had a gradual clinical improvement over time.In contrast, patients from MAL-PDT group had a rapid clinical improvement with total response at week 10. 本研究表明红光MAL-PDT治疗的起效迅速。第二周，82.3%的II-IV等级患者变为0-I等级。并且，炎性皮损的中位数从52减少到5，中值百分数减少91.3%。相比之下，在单色红光组中，只有14.2%等级为II-IV的患者等级变为0-I。但是，两种治疗都对炎性和非炎性皮损的改善疗效显著。有趣的是单色红光组患者随着时间的推移有一个渐进的临床改善。与此相反， MAL-PDT组患者有一个快速的临床改善，并在第10周完全好转。 This study shows that both treatments significantly reduce acne severity at 10 weeks of follow-up visits, but MAL-PDT has a quicker onset of action with a higher response than red light alone. Hence, red light plus topical porphyrin precursors enhance the phototherapeutic effects with an earlier clinical improvement. 本研究表明在第10周的随访中，两种治疗都明显降低了痤疮的严重度，但是MAL-PDT比单色红光起效更快，疗效更好。因此，红光外加局部卟啉前体可提高光疗效果，更快改善临床症状。 Also of interest, the red light alone group showed a significant reduction in inflammatory and non-inflammatory lesions. Interestingly, Na et al. assessed the efficacy of red light phototherapy using a portable device in facial acne.Eight weeks after treatment, the percent reduction of total lesions was significantly higher in the treated side (55% reduction) comparedto the control side (19%increase). This study also showed the beneficial effect of red light on inflammatory acne, which has been attributed to greater skin penetration and greater sensitivity of P. acnes and sebaceous glands to photodestruction.This mechanism may explain the significant clinical responseof the red light alone group of our study. 同样地，单色红光组的炎性和非炎性皮损明显减少。有趣的是通过用于面部痤疮的便携式设备，Na等人对红光光动力疗法的疗效进行了评估。治疗后的8周，相比对照侧（增加19%），治疗侧（降低55%）总皮损的降低率明显较高。本研究也指出红光对炎性痤疮产生有益效果，这是由于（红光）有更强的皮肤穿透力，以及痤疮丙酸杆菌和皮脂腺对光裂解的较强的敏感度。该机制可解释本研究中单色红光组明显的临床反应。 Even though the MAL-PDT group had more patients with severe acne, it showed a better response than the red light alone group. This better response is supported by other studies. As such, a study of MAL-PDT and placebo-PDT using red light (37 J/cm2) showed a median percent reduction in inflammatory lesions of 54% and 20% at 12 weeks after treatment,respectively.Other reports from red light MAL-PDT studies have been shown to reduce 59% to 68% of inflammatory lesions at 12 weeks after treatment. In addition,Riddle et al. showed an analysis of 8 trials and 13 case series related to PDTand acne. All reported reduction in inflammatory lesions of 25-88%, with consistent superiority of PDT over light alone. However, these studies used different light dosimetry and irradiance, skin preparation and drug incubation time. To date, non-uniform parameters are being used for wavelength, light dosimetry,skin preparation, type of precursor and concentrationand time of incubation. Therefore, there is no consensus on how to perform PDT for acne treatment. Surely, the modification of these variablesmay affect the efficacy and side effects. Thus, guidelines for PDT in acnetherapy are warranted. 尽管MAL-PDT组有更多严重的痤疮患者，但其疗效好于单色红光组。其他研究也证实了MAL-PDT有更好的疗效。例如，一项关于MAL-PDT和使用红光(37 J/cm2)的安慰剂-PDT的研究显示，治疗后12周炎性皮损的中值百分比下降分别为54%和20%。在其他关于红光MAL-PDT研究报道中，治疗后12周炎性皮损减轻59%到68%。此外，Riddle等人分析了与PDT和痤疮相关的8次试验和13个案例系列。所有研究都报道了炎性皮损降低25-88%，PDT的降低率始终远超单色光疗法。但是这些研究使用了不同的光剂量和辐照度，备皮和药物孵化时间。目前，研究中正应用非一致性参数包括波长、光剂量学、备皮、前体类型以及孵化的浓度和时间。因此，如何实施痤疮的PDT治疗未达成共识。当然，修改这些变量也许影响到疗效和副作用。所以，痤疮的PDT疗法指南是正当合理的。 Histological changessuch as reduced numbers of sebocytes, reduced amounts of lipids (green color) and a smaller size of sebaceous glands were found in apatient with moderate acne treated with MAL-PDT. For PDT activation, high intensity red light sources have a deeper penetration than blue light sources(Tyndall effect), and are more likely to reach and activate porphyrins in sebaceous glands. This mechanism can produce sebaceous gland destruction and probably a longer remission of acne. Also, red light PDT can induce a reduction in the size and/or function of the sebaceous glands. Theoretically, this effect can be reversible or more permanent depending on the number of treatment sessions.Assuch, Hongcharu et al. conducted a study of acne patients treated with red light ALA-PDT. The authors reported that sebum excretion was eliminated clinically, and this effect lasted for at least 20 weeks after multiple treatment sessions and 10 weeks after a single treatment. Also, histological findings such as vacuolization of sebocytes and sustained atrophic glands were observed. However, due to the fact that our histopathological findings are based on only one biopsy taken from one patient, we cannot generalize this informationto the other patients. 在用MAL-PDT治疗的中度痤疮患者中，我们发现有病理组织变化，例如皮脂腺细胞体数量减少，脂肪（绿色）减少以及较小型皮脂腺。就PDT激活作用而言，高强度的红光源比蓝光源有更强的渗透力（延德耳效应），并更可能到达且激活皮脂腺里的卟啉。该机制可破坏皮脂腺，且可较长期的缓解痤疮。并且，红光PDT可减少皮脂腺的大小和/或功能。从理论上说，该作用依据疗程数量可能具有可逆性或更持久性。以Hongcharu等人一项红光ALA-PDT治疗痤疮患者的研究为例，作者报道了临床上消除了皮脂分泌，并且该效果在多个疗程后持续了至少20周，在单次疗程后持续了10周。同时，我们观察到了组织学结果，例如皮脂腺液泡化和持续腺体萎缩。但由于该组织学结果是基于对一个患者的一次活检，所以不适用于其他病人。 It seems that red light sources in repeated treatment sessions may produce a higher and long erefficacy along with suppression of sebaceous gland functions. As such, thisapproach would be as efficient as oral retinoids in targeting the sebaceousglands. This theory will be unraveled when PDT is optimized with long-term clinical trials. 在反复疗程中，红光源似乎能产生伴随有抑制皮脂腺功能的更好、更长的疗效。正因如此，在以皮脂腺为靶标上，该疗法和口服异维A酸同样有效。随着长期的临床实验， PDT得以优化，该理论将会被阐明。 In addition, side effects such as pain, erythema and epithelial exfoliation were reported in our study. MAL-PDT treatment was associated with more pain and erythema than red light alone treatment. Intra-group analyses showed that MAL-PDT patients had more severe pain after the second treatment. This situation may be explained by the fact that after illumination there is a superficial burn on the skin surface. Inflammation and epidermalturn over are presented in the damaged skin, so when the second treatment is applied, the skin is thinner and signs of inflammation and epidermal exfoliation can beseen. As such, the skin is more sensitive to illumination, which increases pain and erythema. These side effects have also been reported in other studies. Onthe other hand, sterile pustular eruption was not seen in any patients. 此外，本研究也报道了治疗的副作用，例如疼痛、红斑和上皮脱落。MAL-PDT治疗比单色红光治疗更容易产生疼痛和红斑。组内分析表明接受MAL-PDT治疗的患者在第二次治疗后疼痛更剧烈。这个情况可能是由于光照后造成的皮肤表面浅层烧伤。受损皮肤出现炎症和表皮更新，所以第二次治疗时，皮肤更薄，并可观察到炎症和表皮脱落的迹象。据此，皮肤对光照更敏感，这使得疼痛和红斑增加。其他研究中也报道了这些副作用。另一方面，没有患者出现无菌性脓疱爆发。 Taking into accountthat non-uniform parameters are being used for PDT treatment, there is a need to optimize the treatment protocol to ensure a better result with a long-termacne remission. The results from our study indicate that red light MAL-PDT and red light alone are significantly effective for improving inflammatory andnon-inflammatory lesions. Nevertheless, red light MAL-PDT has a quicker onset of action and a higher response than red light alone. 考虑到PDT治疗使用了非一致性参数，我们需要优化治疗方案以确保更好的疗效，长期延缓痤疮。我们的研究结果表明红光MAL-PDT和单色红光对改善炎性和非炎性皮损疗效显著。不过，红光MAL-PDT比单色红光起效更快，疗效更好。 本文为MediCool小编翻译整理，如果您喜欢这篇文章请点击右上角“...”分享给您的朋友，如果您对我们的皮肤科周讯感兴趣，直接点击“阅读原文”详细了解我们Mediskin皮肤科学术网站，感谢您的支持与关注！ |
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