Disappointing results and low tolerability of photodynamic therapy with topical 5-aminolaevulinic acid in psoriasis. A randomized, double-blind phase I/II study

BACKGROUND: Based on good results in the treatment of superficial skin tumours, since the early 1990s topical photodynamic therapy with aminolaevulinic acid (ALA PDT) has been used for disseminated, inflammatory dermatoses including psoriasis. However, there is still a lack of well-documented trials. OBJECTIVE: A prospective randomized, double-blind phase I/II intrapatient comparison study was conducted in 12 patients to investigate whether topical ALA PDT is an effective treatment for chronic plaque-type psoriasis. METHODS: In each patient three psoriatic plaques were randomly treated with a light dose of 20 J/cm(2) and 0.1%, 1% and 5% ALA, respectively. Treatment was conducted twice a week until complete clearance or for a maximum of 12 irradiations. Therapeutic efficacy was assessed by weekly determination of the psoriasis severity index (PSI). RESULTS: The mean percentage improvement was 37.5%, 45.6% and 51.2% in the 0.1%, 1% and 5% ALA-treated groups, respectively. Irradiation had to be interrupted several times because of severe burning and pain sensation. CONCLUSION: Topical ALA PDT did not prove to be an appropriate treatment option for plaque-type psoriasis due to disappointing clinical efficacy, the time-consuming treatment procedure and its unfavourable adverse event profile.     

The effects of ALA-PDT on microbiota in pilosebaceous units of patients with severe acne: A metagenomic study

Background5-aminolevulinic acid mediated photodynamic therapy (ALA-PDT) is increasingly used to control severe acne. However, its impact on skin microbiota remains uncertain.ObjectivesWe aimed to compare the makeup, diversity, and function of the microbiota in pilosebaceous units of patients with severe acne before and after ALA-PDT.MethodsA longitudinal cohort study was performed on 11 participants with severe facial acne. All patients were given 5%ALA-PDT every two weeks for three sessions in total. The contents of lesions were sampled for metagenomic sequencing at baseline and two weeks after the first ALA-PDT session.ResultsCutibacterium acnes was the most dominant species followed by Staphylococcus epidermidis and Pseudomonas fluorescens. Treatment with ALA-PDT led to clinical improvements in acne severity concurrent with a significant reduction in the relative abundance of C. acnes, while P. fluorescens increased significantly after ALA-PDT. No significant change was identified in other species. ALA-PDT administration was associated with an increased microbiota diversity and reductions in the relative abundance of the functional genes involved in energy metabolism and DNA replication.ConclusionsALA-PDT plays a therapeutic role by killing C. acnes, increasing P. fluorescens and the microbiome diversity, while inhibiting the function of microbiota in pilosebaceous units of severe acne.     

眼睑巨大溃疡型基底细胞癌1例

基底细胞癌是皮肤科常见的恶性肿瘤,根据临床及组织病理一般可以诊断,治疗难度不大,但是一些特殊部位和一些特殊类型的基底细胞癌的治疗比较困难.我科在2010年4月6日收治了1例眼睑下缘巨大溃疡型基底细胞癌老年男性患者,现报告如下: 1 病例摘要 患者,男,63岁.右眼睑下缘皮肤溃疡2年,加重2月.患者20年前右侧眼睑下缘近鼻梁处出现一黄豆大小突起物,遂就诊于当地医院,未予以明确诊断,予以冷冻治疗,治疗后留一疤痕,无其他不适.     

ALA-PDT治疗对瘢痕癌体外培养细胞中MMP-9、MMP-13及TIMP-1水平的影响

目的:研究ALA-PDT治疗对瘢痕癌体外培养细胞中MMP-9、MMP-13和TIMP-1的影响。方法:将瘢痕癌体外培养细胞分为正常组、阴性对照组、高浓度ALA-PDT治疗组、低浓度ALA-PDT治疗组、光动力治疗组。对高浓度ALA-PDT治疗组、低浓度ALA-PDT治疗组、光动力治疗组分别进行干预治疗。于治疗后24h和48h采集样本,进行RT-PCR实验和ELISA实验。结果:治疗组中MMP-9、MMP-13的表达水平在ALA-PDT治疗后24h和48h的瘢痕癌体外培养细胞中的表达水平要明显高于阴性对照组,差异具有显著性(P<0.01),而治疗组中TIMP-1的表达水平要明显低于阴性对照组,差异具有显著性(P<0.01)。高浓度治疗组与低浓度治疗组之间比较有差异(P<0.05)。结论:ALA-PDT治疗可改变瘢痕癌体外培养细胞中MMP-9、MMP-13和TIMP-1的表达,使MMP-9/TIMP-1及MMP-13/TIMP-1之间的比例上调。     

派特灵联合艾拉-光动力治疗尖锐湿疣的临床疗效

目的观察派特灵联合艾拉-光动力治疗尖锐湿疣的临床疗效。方法采用随机对照、平行试验的方法,将143例尖锐湿疣患者随机分为单用派特灵组、单用艾拉-光动力组及派特灵和艾拉-光动力联合用药组,治疗3个月观察疗效。结果联合用药组临床痊愈率为91.67%（44/48）,单用派特灵组为70.00%（35/50）,单用艾拉-光动力组为66.67%（30/45）;联合用药组复发率为6.25%（3/48）,单用派特灵组为24.00%（12/50）,单用艾拉-光动力组为22.22%（10/45）,3组间不良反应差异无统计学意义。结论派特灵联合艾拉-光动力治疗尖锐湿疣疗效明显优于单用药,复发率低,安全性好。     

Evaluation of photodynamic therapy using topical aminolevulinic acid hydrochloride in the treatment of condylomata acuminata: a comparative, randomized clinical trial

Objectives: To determine the safety and efficacy of photodynamic therapy (PDT) with topical application of 20% wt/vol aminolevulinic acid hydrochloride (ALA) in the treatment of condylomata acuminata (CA). Study design: Patients with CA were randomly allocated into the ALA‐PDT group and the CO₂ laser group in an allocation ratio of 3 : 1. The treatment was repeated weekly if necessary, but no more than 3 times. The primary efficacy endpoint was the wart clearance rate 1 week after the last treatment. The recurrence rate was evaluated at weeks 4, 8 and 12 after the treatment ended. The clinical response to therapy and adverse effects were recorded. Results: A total of 91 patients with CA were enrolled in the clinical trial. Of these 90 (98.9%) patients completed the trial (67 in the ALA‐PDT group, and 23 in CO₂ laser group). By 1 week after the last treatment, the complete clearance rate was 95.93% in the ALA‐PDT group and 100% in CO₂ laser group (P>0.05). The clearance rate of CA at male urethral orifice was100% in the ALA‐PDT group and 100% in the CO₂ laser group (P>0.05). The overall recurrence rate calculated by the end of the entire follow‐up period was significantly lower in the ALA‐PDT group than that in the CO₂ laser group (9.38% vs 17.39%, P<0.05). Moreover, there was no systemic adverse event in either group. The proportion of patients with adverse effects in the ALA‐PDT group (8.82%) was also significantly lower than that in the CO₂ laser group (100%, P<0.05). The side‐effects in patients treated with ALA‐PDT mainly included mild burning and/or stinging restricted to the illuminated area. Conclusion: The results confirmed that topical application of ALA‐PDT is a simpler and as effective therapy with a lower incidence of adverse effects in the treatment of CA compared with conventional CO₂ laser therapy.     

Tissue distribution and kinetics of endogenous porphyrins synthesized after topical application of ALA in different vehicles.

The use of 5-aminolaevulinic acid (ALA) is gaining increasing attention for photosensitization in photodynamic therapy of superficially localized tumours. The aim of this work was to determine the kinetics of porphyrin generation in tissues after topical application of ALA delivered in different vehicles on the skin overlying the tumour and normal skin of mice. Maximal accumulation was found in tumour 3 h after ALA application in both cream and lotion preparations. Normal and overlying tumour skin tissues showed different kinetic patterns, reflecting histological changes when the latter is invaded by tumour cells. Liver, kidney, spleen and blood porphyrins also raised from basal levels, showing that ALA and/or ALA-induced porphyrins reach all tissues after topical application. During the first 24 h of ALA topical application, precursors and porphyrins are excreted by both urine and faeces. ALA lotion applied on the skin overlying the tumour induced higher accumulation of tumoural porphyrins than cream, and lotion applied on normal skin appeared to be the most efficient upon inducing total body porphyrins. This work has demonstrated the great influence of the formulation of ALA vehicle on penetration through the skin. Knowledge of the kinetics of porphyrin generation after different conditions of ALA application is needed for the optimization of diagnosis and phototherapy in human tumours.     

5-氨基酮戊酸光动力疗法联合CO_2激光治疗尖锐湿疣的临床观察

目的观察5-氨基酮戊酸光动力(ALA-PDT)疗法联合CO2激光与单纯使用ALA-PDT疗法和单纯使用CO2激光疗法治疗尖锐湿疣的临床疗效。方法将入选的120例尖锐湿疣患者随机分为3组,即ALA-PDT疗法联合CO2激光治疗组、单纯ALA-PDT疗法治疗组和单纯CO2激光治疗组,每组40例,均治疗结束3月后判定疗效。结果 ALA-PDT疗法联合CO2激光治疗组清除率为100%(40/40),痊愈率为90%(36/40),复发率为10.00%(4/40);单纯使用ALA-PDT疗法组痊愈率为42.50%(17/40),复发率为29.17%(7/24);单纯使用CO2激光治疗组一次性清除率为100%(40/40),痊愈率为37.50%(17/40),复发率为62.50%(25/40)。三组患者的痊愈率和复发率比较,ALA-PDT疗法联合CO2激光治疗组均优于单纯ALA-PDT疗法治疗组和单纯CO2激光治疗组,差异均有统计学意义(P均0.001)。结论 ALA-PDT疗法联合CO2激光疗法治疗尖锐湿疣的疗效确切,复发率较低,其疗效优于单纯使用ALA-PDT疗法组和单纯使用CO2激光治疗组,值得临床应用。     

5-氨基酮戊酸光动力疗法联合YAG激光治疗尖锐湿疣效果

目的观察5-氨基酮戊酸光动力疗法（ALA-PDT）联合YAG激光治疗尖锐湿疣（CA）的疗效及复发率。方法将入选的128例CA患者随机分为A组（62例）和B组（66例）,A组单纯YAG激光治疗,B组采用ALA-PDT联合YAG激光治疗,对比两组患者的临床疗效及复发率。结果 A组治愈37例（59.7%）,复发25例（40.3%）;B组治愈54例（81.8%）,复发12例（18.2%）,两组比较差异有统计学意义（P〈0.01）。结论 ALA-PDT联合YAG激光治疗CA治愈率高于单纯YAG激光治疗组,且可降低复发率。     

EGCG对A431细胞NF-κB表达的表观遗传修饰效应及对光动力的影响

目的:研究表没食子儿茶素没食子酸酯（EGCG）对人表皮细胞癌A431细胞内核转录因子（NF-κB）表达的表观遗传修饰效应,探讨联合5-氨基酮戊酸介导光动力疗法（ALA-PDT）的增敏作用。方法:低氧诱导培养A431细胞,用MTT比色法检测不同浓度EGCG对A431细胞增殖的影响,MS(methylation specific)-PCR检测p16INK4ɑ基因甲基化变化,免疫印迹检测NF-κBp65,DNMT1,HDAC1,CyclinD1,HIF-1α,VEGF,p16INK4ɑ表达,并用免疫细胞化学染色观察A431细胞E-钙黏蛋白（E-cadherin）;用流式细胞仪检测EGCG联合ALA-PDT诱导的A431细胞凋亡。结果:EGCG具有抑制A431细胞增殖并诱导凋亡的作用,抑制效应呈浓度依赖性;p16INK4ɑ基因甲基化水平减低显著;免疫印迹显示NF-κBp65,DNMT1,HDAC1,CyclinD1,HIF-1α,VEGF表达下调,p16INK4ɑ表达上调;E-cadherin表达上调显著,呈浓度依赖性。EGCG联合ALA-PDT治疗组促凋亡作用显著。结论:EGCG对A431细胞具有抑制增殖、血管生成、侵袭的作用,通过影响NF-κB表观遗传修饰诱导细胞凋亡。EGCG联合ALA-PDT的促凋亡作用,增强了A431细胞对ALA-PDT的敏感性。