Photodynamic therapy for acne vulgaris: a randomized, controlled, split-face clinical trial of topical aminolevulinic acid and pulsed dye laser therapy

Background  There remains the need for more effective therapeutic options to treat acne vulgaris. Interest in light-based acne treatments has increased, but few randomized, controlled clinical trials assessing the value of photodynamic therapy (PDT) for acne have been reported.
Aims  We sought to examine the efficacy of PDT using 5-aminolevulinic acid (ALA) and pulsed dye laser therapy in the treatment of acne.
Patients/methods  We conducted a randomized, controlled, split-face, single-blind clinical trial of 44 patients with facial acne. Patients were randomized to receive three pulsed dye laser treatments to one side of the face after a 60–90 min ALA application time, while the contralateral side remained untreated and served as a control. Serial blinded lesion counts and global acne severity ratings were performed.
Results  Global acne severity ratings improved bilaterally with the improvement noted to be statistically significantly greater in treated skin than in untreated skin. Erythematous macules (remnants of previously active inflammatory lesions) decreased in number in treated skin when compared with control skin and there was a transient but significant decrease in inflammatory papules in treated skin when compared with untreated skin. There were no other statistically significant differences between treated and untreated sides of the face in terms of counts of any subtype of acne lesion. Thirty percent of patients were deemed responders to this treatment with respect to improvement in their inflammatory lesion counts, while only 7% of patients responded in terms of noninflammatory lesion counts.
Conclusions  PDT with the treatment regimen employed here may be beneficial for a subgroup of patients with inflammatory acne.     

The practicalities of photodynamic therapy in acne vulgaris

A staple clinical skill in a dermatologist’s repertoire is the ability to treat acne vulgaris effectively. Light‐based therapies such as photodynamic therapy (PDT) widen the therapeutic options available for acne. Numerous review articles have agreed on the answer to core questions such as: ‘Does PDT work?’ and ‘Which acne lesions respond best to PDT?’ They conclude that PDT is especially useful in inflammatory acne and may be superior to light therapy alone. This literature review seeks to offer guidance regarding treatment‐specific queries about the photosensitizer, route of administration, treatment intervals, light sources and patient selection. Ovid Medline, PubMed and EMBASE database searches were executed between January 2007 and March 2008. Due to the scarcity of data, all five randomized trials, four of which were at least investigator blinded and controlled, 12 open clinical studies, two case reports and two abstracts published in English were considered. Four hundred and nineteen patients were recruited. As the quality of the data was suboptimal in a significant number of articles, the conclusions are drawn in very broad strokes: topical short‐contact (90 min or less) 5‐aminolaevulinic acid or methyl aminolaevulinate using a noncoherent light source at 2–4‐week intervals for a total of two to four treatments produces the greatest clinical effect. Papulopustular acne is more responsive and all Fitzpatrick skin types are eligible. However, patients with skin types I–III have a reduced risk of postinflammatory hyperpigmentation seen in darker skin types. These treatment parameters demonstrate a good side‐effect profile resulting in acne remission for at least 3 months to a year in a relatively cost‐effective manner. Well‐designed nonsplit‐face randomized controlled trials would offer further guidance, especially for queries surrounding the light source and illumination schemes.     

Photodynamic therapy with violet light and topical δ-aminolaevulinic acid in the treatment of actinic keratosis, Bowen's disease and basal cell carcinoma

BACKGROUND: Most clinical studies using photodynamic therapy (PDT) with topical application of delta-aminolaevulinic acid (delta-ALA) use red light because it allows greater depth of penetration. However, given the porphyrin-like spectrum of delta-ALA-induced photosensitivity, violet light provides a maximal overlap with the excitation spectrum of protoporphyrin IX, meaning that PDT with violet light uses less light energy to induce the phototoxic reaction. AIM: To study the efficacy of violet light in combination with topical delta-ALA PDT in the treatment of pre-malignant and malignant skin lesions. METHODS: Eight hours after 20% delta-ALA was applied topically, photoirradiation was performed with an incoherent light source (Philips HPM-10, 400 W) emitting predominantly violet light (400-450 nm). Lesions received 10-20 J/cm2 during an exposure time of 30 min. The 38 subjects treated included three with basal cell naevus syndrome with multiple (> 30) superficial and nodular basal cell carcinomas (BCCs), one subject had multiple lesions of Bowen's disease, involving 50% of the scalp, and the remaining 34 subjects presented a total of 35 superficial BCCs, 10 nodular BCCs, four large solar keratoses and five solitary lesions of Bowen's disease. RESULTS: Complete remission both clinically and histologically was seen after a single treatment in 82% of the superficial BCCs (100% after a second treatment), 50% of the nodular BCCs, one of the four solar keratosis lesions (partial remission in the other three) and 90-100% of the solitary lesions of Bowen's disease. CONCLUSIONS: delta-ALA PDT using violet light appears to be a well tolerated and effective alternative treatment for premalignant and malignant skin lesions, especially when there are multiple lesions or large patches comprising a large area of skin.     

Photodynamic therapy of acne vulgaris using 5‐aminolevulinic acid 0.5% liposomal spray and intense pulsed light in combination with topical keratolytic agents

Background Increasing antibiotic resistance of Propionibacterium acnes and growing awareness on the side effects of topical and systemic drugs in the treatment of acne vulgaris by physicians and patients have paved the way for a search into new efficacious and safe treatment modalities such as photodynamic therapy (PDT). Although the efficacy of PDT using 20% 5‐aminolevulinic acid (ALA) cream has been established, phototoxic side effects limit its use. The 5‐ALA concentration can be lowered by a factor of 40 by changing the vehicle of 5‐ALA from a moisturizing cream to liposome encapsulation. Objectives Assessment of the efficacy and the safety of PDT using 5‐ALA 0.5% in liposomal spray and intense pulsed light (IPL) in combination with topical peeling agents (Li‐PDT‐PC) in acne vulgaris. Materials and Methods 32 patients suffering from acne participated in this randomized, prospective, single blind study. All patients were treated with Li‐PDT‐PC. During the study nine patients were additionally treated with topical or systemic antibiotics (Li‐PDT‐PC‐AT). These patients were removed from the study although their results were recorded. Results After a mean period of 7.8 months and a mean number of 5.7 treatments the mean total number of lesions dropped from 34.6 lesions to 11.0 lesions, resulting in a mean improvement of 68.2%. Side effects were minimal. Additionally, an intention to treat analysis was conducted. Conclusion Photodynamic therapy of acne vulgaris using 5‐ALA 0.5% liposomal spray and IPL in combination with topical peeling agents is safe and efficacious, even in patients with acne recalcitrant to standard therapy.     

Photodynamic therapy with intralesional 5-aminolevulinic acid and intense pulsed light versus intense pulsed light alone in the treatment of acne vulgaris: a comparative study

Despite the availability of many treatment modalities for acne vulgaris (AV), few of which provide excellent results. Photodynamic therapy (PDT) was shown to be an effective treatment especially when used with topical 5-aminolevulenic acid (ALA). We compared the efficacy and safety of PDT using intralesional ALA (IL-ALA) with intense pulsed light (IPL) and IPL alone in the treatment of AV. This study was carried on 30 patients with nodulocystic and inflammatory AV on the face and back. The right side of the body was treated with IL-ALA plus IPL, while the left side was treated with IPL alone. All patients experienced a reduction in number of acne lesions on both sides of the body, but the reduction was significantly more in PDT side than IPL only side. Recurrence of the lesions was significantly more likely in the IPL only side. There was no statistically significant difference between the face and back lesions in drug side effects and recurrence of the lesions. We concluded that photodynamic therapy in this cohort is effective in the treatment of AV when combined with IL-ALA. It gives superior results compared with IPL alone with minimal and tolerable side effects and less recurrence rates.     

Topical aminolevulinic acid-photodynamic therapy for the treatment of acne vulgaris

BACKGROUND: Photodynamic therapy (PDT) is useful for the treatment of epidermal neoplasia but may also have use in the treatment of inflammatory dermatoses. The purpose of this study was to evaluate the safety and efficacy of PDT in the treatment of acne on the face. METHODS: Eight patients with mild-to-moderate acne vulgaris on the face were treated with one session of topical aminolevulinic acid (ALA)-PDT using a red light. Each patient's face was divided into two areas (right side and left side) for ALA-PDT and untreated control. Twenty percent topical ALA was applied with 4 h occlusion, and 18 J/cm(2) red light (630+/-63 nm) was administered. Each patient's acne was visually assessed by a spot count of both inflamed and non-inflamed lesions at baseline and at 1, 3, and 6 months following PDT. RESULTS: At 1, 3, and 6 months, the mean percentage reduction in inflamed lesions count was 27.6%, 37.9%, and 41.9%, respectively, in the ALA-PDT-treated area, whereas in the control area, it was 8.0%, 14.7%, and 15.4%, respectively, compared with the baseline. This showed a higher reduction of a spot count of inflamed lesions in the ALA-PDT-treated area, which was statistically significant (P<0.05). There was a slightly higher reduction of a spot count of non-inflamed lesions in the ALA-PDT-treated area, which was statistically not significant (P>0.05). The adverse effects were minimal. CONCLUSION: ALA-PDT with red light was found to be effective in the reduction of the number of inflamed lesions in patients with mild-to-moderate acne vulgaris, with no significant short-term adverse effects.     

Photodynamic therapy for inoperable vulval Paget's disease using δ-aminolaevulinic acid: successful management of a large skin lesion

A 74-year-old woman with extensive inoperable vulval extramammary Paget's disease who had lymph node and pulmonary metastases, was treated with etoposide (VP16) 100 mg and 5000 cGy electron beam irradiation, which reduced the lesion by 60%. Following these interventions, the residual lesion was successfully treated with repeated photodynamic therapy using delta-aminolaevulinic acid, which achieved a nearly complete remission.     

0.5% Liposome-encapsulated 5-aminolevulinic acid (ALA) photodynamic therapy for acne treatment

Abstract

Background: Photodynamic therapy using topical 5-aminolevulinic acid (ALA) has been successful in treating acne vulgaris, but sun avoidance for at least 48 hours after treatment is necessary due to the risk of post-treatment photosensitivity. Recently, a lower concentration of liposome-encapsulated 5-ALA was introduced to minimize this risk. Objectives: To evaluate the efficacy and safety of liposome-encapsulated 0.5% 5-ALA in the photodynamic therapy of inflammatory acne and its effects on sebum secretion in Asian skin. Methods: Thirteen Korean subjects with inflammatory acne were administered 0.5% ALA spray before photoradiation treatment. Photoradiation was performed at 3.5–6.0 J/cm² three times during each of two visits, performed 2 weeks apart. Improvement of acne was evaluated subjectively and objectively based on the Korean Acne Grading System. Sebum secretion was measured quantitatively at each visit. Results: The mean reduction in acne grade at the end of the treatment was 43.2%. Of the patients, 69.2% reported improvements in subjective skin oiliness, but fewer showed objective reductions in sebum secretion as determined by the Sebumeter^® SM10. No serious adverse events were observed. Conclusion: Photodynamic therapy using liposome-encapsulated 0.5% 5-ALA improved inflammatory acne with minimal side effects in Asians.     

Prospective study of topical 5‐aminolevulinic acid photodynamic therapy for the treatment of severe adolescent acne in Chinese patients

Acne vulgaris is one of the most common skin diseases in adolescents. In the present study, we aimed to evaluate the effectiveness and safety of topical 5‐aminolevulinic acid (ALA)‐mediated photodynamic therapy (PDT) for the treatment of severe acne in Chinese adolescent patients. Twenty‐one Chinese adolescent patients aged 12–18 years with Pillsbury III–IV severe facial acne were treated with three courses of ALA‐PDT. A 5% ALA lotion was applied topically for 60 min followed by irradiation with light‐emitting diode light at 633 nm with a light intensity of 75–80 mW/cm² and a light dose of 90–96 J/cm². Clinical assessment was conducted before and after each treatment, and at each follow‐up session. The total effective rates were 85.71%, 90.48%, and 95.23% after the three PDT sessions, and at the 4‐ and 8‐week follow ups, respectively. ALA‐PDT is an effective treatment for severe adolescent acne vulgaris, and is associated with mild and reversible side‐effects.     

Efficacy of ALA-PDT vs blue light in the treatment of acne

BACKGROUND: Photodynamic therapy (PDT) is based on the principle of using light excitation of a wavelength-specific endogenous or exogenous photosensitizer to destroy the target tissue, and has shown efficacy in the treatment of certain non-melanoma skin cancers. PDT using aminolevulinic acid (5-ALA) has attracted attention in the treatment of acne vulgaris. METHOD: Twenty patients with moderate to severe acne vulgaris on the face were treated with four sessions of topical ALA-PDT with blue light (415 nm) on the right side of the face compared with blue light alone on the left side of the face, each treatment being 1 week apart. Ten percent of topical ALA was applied to acne spots on the right side of the face with a 1-h incubation period and the entire face was treated with 48 J/cm(2) of 415 +/- 5 nm light from an articulated LED planar array. Evaluation was performed by counting acne lesions at baseline, 4, 8, 12 and 16 weeks after the beginning of the treatment. Biophysical measurements included sebum levels and the erythema, and melanin indices. RESULT: At the given assessment times 4, 8, 12 and 16 weeks after the beginning of the treatment, the mean percent reduction in inflamed lesions counts tended to be higher in the ALA-PDT areas; it was 32%, 50.9%, 65.9% and 71.1%, respectively, compared with the blue-light-alone treatment, which was 20.7%, 27%, 57.7% and 56.7%, respectively, but without any statistical significance (P=0.092). There was no demonstrable significant change in sebum excretion, erythema or the melanin index after treatment. The side effects were pain, stinging, peeling, erythema, pruritus, oozing and pustules. These side effects were stronger on the ALA-PDT-treated side. CONCLUSION: From this study, the trend for ALA-PDT with blue light to be superior to blue light alone was observed, but it did not reach statistical significance. ALA-PDT had more side effects.     

Improved efficacy and tolerability of retinoic acid in acne vulgaris: a new topical formulation with cyclodextrin complex ψ

OBJECTIVES: Retinoic acid (RA) has long been used, both topically and systemically, for disorders of keratinization, acne and related disorders. In the present study, the efficacy and tolerability of topical RA prepared as a cyclodextrin beta complex (beta-CD) is investigated in 66 acne vulgaris patients. METHODS: This randomized, double-blind, placebo-controlled study compares nightly topical application of RA/beta-CD complex hydrogel formulation (0.025%), RA/beta-CD complex in moisturizing base (0.025%), hydrogel base, moisturizer base or a commercial RA gel (0.05%) in acne vulgaris patients. Improvement of acne was assessed using a 5-point improvement scale and by measuring sebum and moisture content of the skin using an SM 810 sebumeter/corneometer. RESULTS: After 3 months of treatment, mean scores of acne improvement on the 5-point scale were 4 with the RA/beta-CD complex hydrogel formulation, 4.1 with the RA/beta-CD complex in moisturizing base, 1.2 with hydrogel placebo base, 1.1 with moisturizer placebo base and 3 with the commercial RA product. All patients treated with the commercial product experienced local side-effects. One patient discontinued due to severe irritation. None of the patients treated with the RA/beta-CD complex in the moisturizing base and hydrogel formulation experienced significant local irritation, although the sebum content of the skin decreased after application of the RA/beta-CD preparations. This change was not significant compared to controls. The moisture content of the skin was better preserved in the group treated with the RA/beta-CD complex in the moisturizing base. CONCLUSION: The topical RA/beta-CD complex, in hydrogel and moisturizing base, was more effective than the twice concentrated commercial RA product. There were few topical side-effects with this new formulation, which increases patient compliance. Topical RA/beta-CD (0.025% RA) did not significantly reduce sebum secretion but may help to preserve optimum epidermal moisture content with the proper base formulation. This is the first study in the literature reporting efficacy and tolerability of the topical RA/beta-CD complex in acne vulgaris. We conclude that the topical RA/beta-CD complex displays an improved efficacy and tolerability profile and is an effective treatment alternative for acne vulgaris.     

果酸联合丹参酮治疗痤疮疗效评价

目的:评价果酸联合丹参酮治疗寻常痤疮的疗效。方法:90例寻常痤疮患者随机分成两组,治疗组采用果酸治疗,每周2次,同时口服丹参酮胶囊,4粒/次,3次/d;对照组单纯用果酸治疗,8周后观察疗效。结果:治疗组有效率为80.43%,对照组为61.36%,两组疗效比较差异有显著性(P0.05),两组均未发现明显不良反应。结论:果酸联合丹参酮治疗寻常痤疮疗效较好。     

Light/laser therapy in the treatment of acne vulgaris

Acne vulgaris is one of the most prevalent skin diseases known. As common as this condition is, the social and psychological consequences are limitless. Although current treatments are available and include topical or oral antibiotics, it is crucial to develop a less risky and more effective therapy such as light/laser therapy. This article focuses specifically on the benefits of the light/laser treatment on acne vulgaris. Porphyrins accumulated in the bacteria, Propionibacterium acnes, one of the etiologic factors involved in the pathogenesis, allows phototherapy to be a successful modality. They have specific absorption peaks at which lasers have optimal effects. The longer the wavelength of the light is, the deeper its penetration and thus the greater its damage to the sebaceous glands. Although blue light is best for the activation of porphyrins, red light is best for deeper penetration and an anti-inflammatory effect. Ultraviolet (UV) light, although it may have initial an anti-inflammatory effects, has been proven to be potentially carcinogenic and have adverse effects such as aging (by UV-A) and burning (by UV-B). Previous studies indicate successful long-term intervention and selective damage of the sebaceous glands by using a diode laser with indocyanine green (ICG) dye. Mid-infrared lasers have been found to decrease lesion counts while also reducing the oiliness of skin and the scarring process. Nonablative laser treatment of acne scars using the Er:YAG laser with a short-pulsed mode has been successful in reducing the appearance of scars by stimulating neocollagenesis. The light/laser therapy has started to be explored with promising results in highly selected patients that require further investigation in greater populations and well-designed protocols.     

光动力疗法治疗寻常痤疮的研究进展

寻常痤疮是临床上最常见的皮肤病之一,是一种由多因素综合作用引起的,累及毛囊皮脂腺的慢性炎症性皮肤病,其发病率呈逐年上升的趋势,并且影响患者的生活质量.传统的治疗方法为局部或系统治疗,具有潜在的毒副作用,加之细菌对抗生素耐药性的不断增加.近年来,光动力疗法已广泛应用于痤疮的治疗中,并成为治疗痤疮的有效方法,尤其是针对炎症性痤疮,其疗效优于单独光照治疗.光动力疗法的光源主要有二极管激光、强脉冲光、蓝光、红光.研究结果显示,该疗法安全、有效,不良反应较小.     

In vitro and in vivo comparison of two different light sources for topical photodynamic therapy

BACKGROUND: Photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) is an effective and safe treatment option for the treatment of actinic keratosis (AK). Incoherent lamps are often used, matching the absorption maxima of ALA. OBJECTIVES: A comparative trial was performed to evaluate the efficacy of recently developed light-emitting diodes (LEDs). METHODS: Human epidermal keratinocytes were incubated for 24 h with ALA (100, 200, 300, 400 or 500 micromol L(-1)) and irradiated consecutively using either an incoherent halogen lamp (lambda(em) = 580-750 nm; 24 J cm(-2); 40 mW cm(-2)) or an LED system (lambda(em) = 633 +/- 3 nm; 3, 6, 12 or 24 J cm(-2); 40 mW cm(-2)). Topical ALA-PDT was performed on 40 patients with AK (n = 584) in a symmetrical distribution suitable for two-sided comparison. After incubation with ALA (20% in cream base) irradiation was performed with the incoherent lamp (100 J cm(-2); 160 mW cm(-2)) on one side and the LED system (40 J cm(-2); 80 mW cm(-2)) on the opposite side followed by re-evaluation up to 6 months. RESULTS: No significant differences between the LED system (3, 6, 12 or 24 J cm(-2)) and the incoherent light source (24 J cm(-2)) regarding cytotoxicity was found in vitro. The complete remission rate yielded in the in vivo investigation was also not significantly different at 6 weeks (P = 0.95), 3 months (P = 0.75) and 6 months (P = 0.61) following therapy. Six weeks following therapy complete remission rates of 84.3% (LED system) and 82.8% (incoherent lamp) were achieved. There was also no significant difference between both light sources regarding pain during light treatment (P = 0.67), patient satisfaction (P = 1.0) or cosmesis (P = 1.0) following therapy. CONCLUSIONS: These results show the efficacy of an LED system for ALA-PDT both in vitro and in vivo. ALA-PDT with the LED system showed a noninferiority regarding the clinical outcome in the treatment of AK compared with the incoherent lamp.